SAR Journal of Medical Biochemistry

Abbreviated Key Title: SAR J Med Biochem

Home page: https://sarpublication.com/journal/sarjmb/home ISSN 2707-7721 (P)
ISSN 2709-6882 (O)
DOI: 10.36346/sarjmb.2024.v05i03.003

O ri gi n al Rese arch Art i cl e

Diclofenac Induced Hepatorenal Toxicity on Albino Rats: The Assessment

of Mitigative Potential of Fermented Carica Papaya Juice
Arhoghro Ejovwoke Marcellinus1*, Eric Emmauel Uchenna2, Berezi E. Peter3, Madock Obebinaru Joshua1, Agberia
Steve Obruche1, Owotgwun Kasirotu Levi1, Eriomala Ejiroghene Tamaratenane1
1Department of Biochemistry, Faculty of Basic Medical Sciences, College of Health Science, Niger Delta University, Wilberforce Island,
Amassoma, Bayelsa State, Nigeria
2Department of Medical Laboratory Science, Faculty of Basic Sciences, College of Health Science, Niger Delta University, Wilberforce

Island, Amassoma, Bayelsa State, Nigeria

3Department of Chemistry, Isaac Jasper Boro College of Education, Sagbama, Bayelsa, Nigeria

*Corresponding Author: Arhoghro Ejovwoke Marcellinus

Department of Biochemistry, Faculty of Basic Medical Sciences, College of Health Science, Niger Delta University, Wilberforce Island,
Amassoma, Bayelsa State, Nigeria

Article History: | Received: 19.01.2024 | Revised: 09.02.2024 | Accepted: 09.04.2024 | Published: 15.05.2024 |

Abstract: In a study investigating the protective effects of an extract on diclofenac-induced liver and kidney injuries in
Wistar rats, twenty healthy adult Wistar rats weighing between 110g to 200g were randomly divided into four groups of
five rats each. Group 1 Control group: received distilled water and standard feed, Group 2 Diclofenac group:
administered 10mg/kg body weight of diclofenac., Group 3 Diclofenac + Pawpaw extract group: received diclofenac
and post-treated with 200mg/kg body weight of fermented unripe Carica papaya juice, and Group 4 Pawpaw extract
group: administered 200mg/kg body weight of fermented unripe Carica papaya juice. The plant extract and diclofenac
were orally given over a duration of fourteen (14) days. After the treatment was finished, samples of blood and tissue
were collected to analyze the liver function parameters (superoxide dismutase, catalase, and glutathione reductase)
(Alanine aminotransferase - ALT, and alkaline phosphatase - ALP), renal function parameters (creatinine), oxidative
stress markers, and for histological evaluation. The results showed that diclofenac administration caused a significant
increase (p<0.05) in serum levels of ALT and ALP, creatinine and a significant decrease (p<0.05) in antioxidant enzymes
(superoxide dismutase, catalase, and glutathione reductase) compared to the control group. However, treatment with
FUPJ significantly reduced (p<0.05) the levels of ALT and ALP, creatinine, and MDA and increased (p<0.05) the levels
of antioxidant enzymes. In conclusion, FUPJ has the potential to ameliorate diclofenac-induced hepatic and renal
dysfunction through its antioxidant and anti-inflammatory properties.
Keywords: Fermented unripe pawpaw juice diclofenac oxidative stress markers hepatorenal.
Copyright © 2024 The Author(s): This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International
License (CC BY-NC 4.0) which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original
author and source are credited.

1. INTRODUCTION liver contribute to the functions of the hematopoietic

The kidney and liver play vital roles in the body system (Alabi and Akomolafe, 2020). Drug-induced
as they are responsible for regulating electrolytes, acid- injuries frequently affect the liver and kidneys due to
base balance, and blood pressure. They also act as natural their role in metabolism, detoxification, storage, and
filters, removing drugs and toxic waste materials from elimination of medicines and their byproducts. Drugs can
the body system. Additionally, these organs produce harm these crucial organs. (Alabi and Akomolafe, 2020)
hormones and are involved in the production and Nephrotoxicity and hepatotoxicity are significant
metabolism of prostaglandins through cyclooxygenase medical conditions resulting from the administration of
(COX), with the kidney playing a particularly significant specific medications, such as nonsteroidal anti-
role in this process. Furthermore, both the kidney and inflammatory drugs (NSAIDs) (Alabi and Akomolafe,

Citation: Arhoghro Ejovwoke Marcellinus, Eric Emmauel Uchenna, Berezi E. Peter, Madock Obebinaru Joshua, Agberia Steve
Obruche, Owotgwun Kasirotu Levi, Eriomala Ejiroghene Tamaratenane (2024). Diclofenac Induced Hepatorenal Toxicity on Albino
Rats: The Assessment of Mitigative Potential of Fermented Carica Papaya Juice, SAR J Med Biochem, 5(3), 22-29.
22
Arhoghro Ejovwoke Marcellinus et al; SAR J Med Biochem; Vol-5, Iss- 3 (May-Jun, 2024): 22-29.

2020; Störmer et al., 2022). As a nonsteroidal anti- antihypertensive, and anticancer properties (Ugbogu et
inflammatory drug (NSAID) from the phenylacetic acid al., 2023). Research in the field of medicinal plant
class, diclofenac (DF) can reduce swelling and pain, materials remains an important focus, as continuous
block pain signals, lower body temperature, and kill investigations investigate the wide range of health
bacteria. People extensively use methotrexate to manage advantages and therapeutic potentials offered by natural
rheumatoid arthritis and pain; however, it is associated treatments. The focus on herbal medicine is in
with significant adverse effects such as pulmonary, accordance with the growing acknowledgment of the
cardiac, hepatic, and renal tissue destruction, as well as importance of traditional and plant-derived therapies in
gastrointestinal toxicity (Alabi and Akomolafe, 2020; contemporary healthcare methodologies (Ugbogu et al.,
Störmer et al., 2022). Diclofenac, a multitargeted 2023).
medicine, has demonstrated effects on various body
organs, including the lung, stomach, kidney, liver, and The Carica genus belongs to the Caricaceae
heart. This confirmation comes from studies conducted family and is known for its solitary, somewhat woody,
by Alabi and Akomolafe in 2020, Störmer et al., in 2022, large herbaceous plants that grow rapidly and have
and Abiola et al., in 2019. It's not completely clear how indeterminate growth. During its first year of growth, it
diclofenac hurts the kidneys and liver, but it has has the potential to attain a height of 3 meters (Saeed et
something to do with damaging mitochondria, messing al., 2014; Koul et al., 2022).
up the immune system's defenses, making reactive
oxygen species, and stopping enzymes and non-enzyme The Carica papaya is the sole species within the
antioxidants from working in the kidney and liver (Alabi Carica genus. The Caricaceae family is quite prevalent in
and Akomolafe, 2020; Stormer et al., 2022; Abiola et al., the neotropics, with six genera and a minimum of 35
2019). species. The transmission of the disease has reached
numerous tropical and subtropical locations worldwide
Metabolites of diclofenac, such as 4', 5- (Saeed et al., 2014; Koul et al., 2022). The plant
hydroxydiclofenac, can also cause the infiltration of produces large palmate leaves measuring 0.6 square
neutrophils in hepatic cells. To summarize, diclofenac is meters. These leaves possess five to no pinnate lobes,
a commonly utilized nonsteroidal anti-inflammatory with widths ranging from 40 to 60 centimeters. The
drug (NSAID) that has therapeutic advantages but also growth rate of the papaya plant is rapid, with a duration
presents significant adverse effects, such as of 3–8 months from the germination of its seeds to the
nephrotoxicity and hepatotoxicity. The precise onset of flowering, and a further 9–15 months until it is
mechanism by which diclofenac causes kidney and liver ready for harvest (Saeed et al., 2014; Koul et al., 2022).
toxicity is not entirely understood. Nonetheless, it is
associated with mitochondrial harm, disruption of Carica papaya, commonly referred to as
immune-mediated protective processes, generation of papaya, is a tropical fruit that offers a multitude of health
reactive oxygen species, and suppression of enzymatic advantages. The substance contains a high concentration
and non-enzymatic antioxidants in the kidney and liver of antioxidants, as well as vitamins A, B, C, and E, and
tissues (Alabi and Akomolafe, 2020; Störmer et al., minerals including potassium, magnesium, and calcium
2022; Abiola et al., 2019).Throughout history, there has (Saeed et al., 2014; Koul et al., 2022). The fruit is a
been a plentiful supply of medicinal resources obtained highly beneficial source of dietary fiber, which promotes
from plants, which have played a vital role in the efficient digestion and mitigates the risk of constipation
treatment and control of many ailments (Anitha et al., (Saeed et al., 2014; Koul et al., 2022). Herbal therapy
2018). Herbal sources of active chemicals have become utilizes papaya plant leaves for their ability to eradicate
more prominent since they are considered safer and more intestinal parasites and their antioxidant qualities (Saeed
effective than synthetic medications, which are et al., 2014; Koul et al., 2022). Papaya has demonstrated
sometimes linked to environmental issues. The use of anti-inflammatory, antibacterial, anticancer, and
herbal medicines is a manifestation of a worldwide hepatoprotective properties (Saeed et al., 2014; Koul et
resurgence in herbal medicine, indicating an increasing al., 2022). Traditional medicine has utilized papain and
fascination with natural and environmentally-friendly chymopapain, two enzymes found in the fruit and its
healthcare alternatives. The citation for this information seeds, to treat digestive diseases and inflammation
is from Roshan et al. (2014). Plants possess several (Saeed et al., 2014; Koul et al., 2022). Traditional
active constituents that provide therapeutic qualities, and medicine employs the seeds' antiparasitic qualities to
the concentration of these constituents differs among treat intestinal parasites and other gastrointestinal
different plant forms. The bioactive chemicals are illnesses (Saeed et al., 2014; Koul et al., 2022). In
accountable for inducing physiological alterations in the addition to its health benefits, the food industry uses
body, resulting in therapeutic outcomes (Srivastava and papaya as a natural food preservative and a source of
Singh, 2016). The pharmacological significance of pectin. Jams and jellies use pectin as a material (Saeed et
Carica papaya, also known as papaya, has prompted al., 2014; Koul et al., 2022). The fruit's antioxidant and
extensive research. It has demonstrated several anti-inflammatory characteristics make it a valuable
beneficial effects, such as anti-inflammatory, anti- ingredient in cosmetics and skincare products (Saeed et
fertility, hepatoprotective, wound healing, al., 2014; Koul et al., 2022).

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The Carica papaya plant yields fermented transported to the laboratory in Niger Delta University
papaya, which offers a variety of health benefits. It is rich for use.
in antioxidants, phenolic compounds, carotenoids, and
vitamins A, B, C, and E. These components support Fermented unripe pawpaw juice Extract Preparation
digestive health and help reduce oxidative stress. The Unripe Carica papaya fruits underwent a
proteolytic enzymes found in papaya, namely papain and washing process to eliminate any dirt and latex.
bromelain, assist in the digestion process and possess Subsequently, the fruits were peeled and just the flesh
anti-inflammatory properties (Saeed et al., 2014). It is was cut into little pieces. The juice was extracted from
important to exercise caution when consuming unripe fresh fruit using a juice extractor and then immediately
papaya, as it contains papain, which can be potentially cooled on ice to prevent the breakdown of biomolecules
dangerous, particularly for pregnant women. Studies and antioxidants. The UCP juice underwent filtration
have explored the potential benefits of fermented papaya using sterile quality paper (Whatman® grade 1 filter
in battling aging and treating tumors, showcasing paper) and was subsequently stored in closed bottles,
promising results in cancer treatment. The process of away from sunlight, for a duration of 3 days to facilitate
fermentation amplifies the antioxidant characteristics of proper fermentation. After the third day of fermentation,
papaya, hence augmenting its positive effects on health the supernatant was filtered and disposed of The
(Leitão et al., 2022). fermented unripe pawpaw extract was collected, poured
into a container, and kept in the fridge for preservation.
The Carica papaya plant yields fermented
papaya, which offers a variety of health benefits. The Experimental Design
substance is rich in antioxidants, phenolic compounds, The rats were divided into four (4) groups with each
carotenoids, and vitamins A, B, C, and E. These group consisting of 5 rats each.
components support digestive health and help decrease Group 1 (Negative control): Received distilled
oxidative stress. The proteolytic enzymes included in water and pellet feed for14days.
papaya, specifically papain and bromelain, assist in the Group 2 (Test group): Received 10mg/kg per body
digestion process and possess anti-inflammatory weight of diclofenac daily by oral route for 14 days.
properties (THERASCIENCE 2023) (WEBMD 2022). It Group 3 (Test group): Received 10mg/kg per body
is important to be cautious while consuming unripe weight of diclofenac daily by oral route for 14 days
papaya, as it contains papain, which can be potentially and post treated with 200mg/kg body weight of
dangerous, particularly during pregnancy (WEBMD fermented unripe juice of Carica papaya orally for
2023). Researchers have conducted research on 14 days.
fermented papaya to explore its potential benefits in Group 4: Received 200mg/kg body weight of
slowing down the aging process and inhibiting tumor fermented unripe juice of Carica papaya only orally
growth. The findings show promising outcomes in for 14 days.
cancer treatment. The fermentation process enhances
papaya's antioxidant properties, thereby increasing its Twenty-four hours after the final treatment, the
health-promoting benefits (Leitão et al., 2022). animals were weighed again and used chloroform to
render them unconscious. After the treatment concluded,
MATERİALS AND METHODS the rats were sacrificed and blood samples collected via
Animals cardiac puncture to measure liver function parameters
Twenty (20) healthy adult female Wister rats such as Alanine aminotransferase (ALT), and alkaline
weighing between 110g to 200g were obtained from the phosphatases (ALP), renal function parameters like
animal house of Niger Delta University, Amassoma, creatinine, and oxidative stress biomarkers like
Bayelsa state and were allowed to acclimatized for malondialdehyde (MDA), catalase, and superoxide
two weeks during which they were fed with standard dismutase (SOD).
feed (Pellet) and distilled water ad libitum. The rats were
kept in plastic cages at a room temperature of about 27°C Sample Collection
and photoperiodicity of 12-hour light/12-hour dark. The Sample Preparation and Collection
protocols were executed in compliance with the National Blood samples were collected by cardiac
Institutes of Health guidelines for the care and utilization puncture into standard bottles. The blood samples were
of laboratory animals (NIH Publications No. 8023, allowed to clot for 3 hours to enable coagulation.
amended 1978). Afterward, the samples were centrifuged at 2000rpm for
10 minutes, and the supernatant (serum) was collected
Collection and Preparation of Extracts and stored in the refrigerator. The other part was mixed
Collection of Plant with Phosphate buffer and homogenized.
The medicinal plant used in this study was the
fermented juice of unripe Carica Papaya (pawpaw). The Ethics
Unripe Carica Papaya fruits were purchased from The ethical committee at Niger Delta University
Amassoma Market, Bayelsa State, Nigeria. This was in Amassoma, Bayelsa State, Nigeria, authorized all
animal protocols, following the Principles of Laboratory

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Animal Care set forth by the National Institutes of Health from Merck Specialities Pvt. Ltd., India, following the
[NRC]. The animals received compassionate care in line instructions provided in the manufacturer's manual.
with the guidelines outlined in the "Guide for the Care
and Use of Laboratory Animals (1996)" published by the Determination of Markers of Oxidative stress.
National Academy of Sciences. This was by measuring Malondialdehyde (MDA)
[Aebi,1984] and superoxide dismutase
Biochemical Parameters (SOD)[Butler,1963] catalase [Aebi, 1984] as well as
The following biochemical parameters were reduced Glutathione GSH [Sun et al.,1988]
determined spectrophotometrically using the respective
kits and instructions provided in the biochemical kit Statistical Analysis
manual. Data was expressed as Mean ± Standard
deviation. The statistical significance was evaluated by
Estimations of Biochemical Parameters ANOVA using SPSS (Statistical Package for Social
Serum Parameters Sciences). Values were considered statistically
On the 15th day of the research, we euthanized significant when <0.05.
the animals. We collected the blood and stored it in
simple vials for biochemical analysis. The serum was RESULTS
isolated for the determination of liver function The results of the present study are presented in
parameters: aspartate aminotransferase (AST), alanine the Table and bar charts below. Table 3.1 shows the
aminotransferase (ALT), and alkaline phosphatases mean serum levels of ALT, ALP and CREATININE.
(ALP). Enzymatic kits from Accurex Biomedical Figure 3.1 shows the mean tissue homogenate
Limited Pvt. Ltd., India, Renal function parameters: antioxidant activities.
creatinine and urea were determined using standard kits

Table 3.1: Result of the Mean serum level of Alanine aminotransferase and Alanine phosphatase and Creatine
ENZYME PARAMETERS ALT(U/L) ALP(U/L) CREATINE(U/L)
NORMAL CONTROL 71.07±2.24a 128.53±4.21a 0.5±0.03a
DICLOFENAC 141.23±4.51b 160.36±1.79b 0.81±0.02b
DICO + PAWPAW 90.73±3.11c 120.58±7.95d 0.52±0.01c
a
PAWPAW 72.03±3.10 124.33±1.27d 0.5±0.02c

Figure 3.1: The study demonstrated the impact of Diclofenac and fermented Pawpaw on oxidative stress markers
in rats subjected to oxidative stress induction. Group 2, which received Diclofenac, exhibited a statistically
significant decrease (p<0.05) in serum SOD (3.13±0.33), CAT (2.16±0.12), and GSH (2.69±0.58) levels compared to
the control group (group 1). Conversely, MDA levels were significantly higher (p<0.05) in the L-Name treated
group (7.2±0.33) compared to the control group (3.04±0.57)

The data is presented as the mean ± standard Table 3.1 demonstrated that the potential of
deviation (SD). Values with a different superscript from Pawpaw on Diclofenac-induced Liver and kidney
the control group are statistically significant at p < 0.05. dysfunction. Our study found a significant increase in
serum levels of ALT (alanine transaminase), ALP
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Arhoghro Ejovwoke Marcellinus et al; SAR J Med Biochem; Vol-5, Iss- 3 (May-Jun, 2024): 22-29.

(alkaline phosphatase), and creatinine in the In this study, the serum levels showed that
experimental group treated with Diclofenac, compared to Pawpaw has the potential to mitigate diclofenac-induced
the normal control group. Specifically, ALT levels rose liver and kidney dysfunction. There was a significant
to 141.23±4.51, ALP levels to 160.36±1.79, and increase in ALT (141.23±4.51) and ALP (160.36±1.79)
creatinine levels to 0.81±0.02. levels in the group treated with diclofenac compared to
the normal control group. Previous research has linked
However, after administering fermented diclofenac to damage in liver and kidney cells, including
Pawpaw juice at a dosage of 200 mg/kg body weight, we mitochondrial damage, impairment of immune-mediated
observed a notable decrease in these levels compared to protective systems, and inhibition of antioxidants in
the control group. ALT levels decreased to 90.73±3.11, these cells (Kadhim et al., 2022).
ALP levels decreased to 120.58±7.95, and creatinine
levels decreased to 0.52±0.01. The concentrations of ALT (90.73±3.11), ALP
(120.58±7.95), and creatinine (0.52±0.01) in the blood
Post-treatment with 200 mg/kg body weight of dropped compared to the control group after 200 mg/kg
fermented pawpaw juice resulted in a notable reduction body weight of fermented Pawpaw juice was given.
in SOD (6.06±0.17), CAT (4.11±0.13), and GSH Alabi and Akomolafe's 2020 study found that Kolaviron
(5.58±0.38) levels compared to the control group. effectively avoids or minimizes the harmful effects of
Furthermore, MDA levels showed a significant decrease diclofenac in the plasma, liver, and kidney of rats. This
(3.06±0.14) post-treatment with fermented pawpaw implies that Kolaviron can shield the liver and kidneys
juice. All values are presented as mean ± standard from the damaging effects of diclofenac-induced
deviation. hepatorenal toxicity. Additionally, studies have
demonstrated that Artemisia possesses hepatorenal
DISCUSSION protective and preventative properties against
Diclofenac (DF), an NSAID derived from diclofenac-induced liver and kidney damage in rats. The
phenyl-acetic acid, possesses anti-inflammatory, citation "Kadhim et al., 2022" refers to a publication by
analgesic, antinociceptive, antipyretic, and antibacterial Kadhim and colleagues in the year 2022. Studies have
effects. It is commonly used to alleviate symptoms of demonstrated that fermented papaya extract possesses
rheumatoid arthritis and discomfort. Although DF offers antioxidant characteristics and has the potential to
therapeutic benefits, it also has significant and severe safeguard against liver and kidney harm (Leitão et al.,
adverse effects. These encompass harm to the 2022).
pulmonary, cardiac, hepatic, and renal tissues, along with
gastrointestinal toxicity (Alabi and Akomolafe, 2020). Diclofenac and fermented Pawpaw impacted
Diclofenac is a non-threshold multi-targeted medicine some oxidative stress indicators in rats, given the
that has been demonstrated to affect various organs in the diclofenac and fermented Pawpaw oxidative stress
body, such as the heart, lungs, stomach, kidney, and liver induction. Also, when group 2 (the diclofenac-treated
(Alabi and Akomolafe, 2020). group) was compared to group 1 (the control group),
serum SOD (3.13±0.33), CAT (2.16±0.12), and GSH
Diclofenac can hurt mitochondria by messing (2.69±0.58) decreased statistically significantly
up the immune system's defenses, creating reactive (p<0.05). MDA levels in the diclofenac-treated group
oxygen species, and decreasing the activity of enzyme- were significantly (p<0.05) higher than in the normal
and non-enzyme-based antioxidants in the liver and control group (3.04±0.57). Increased kidney MDA and
kidneys (Alabi and Akomolafe, 2020). H2O2 levels demonstrate that diclofenac induces kidney
injury in rats through oxidative damage. This damage is
A study by Owumi and Dim (2015) found that due to the oxidative deterioration of polyunsaturated
drug-induced liver injury is estimated to have an annual fatty acids in kidney membranes (Abiola et al., 2019).
incidence of 10 to 15 per 10,000 to 100,000 persons
exposed to the drug, highlighting the importance of As compared to the control group, post-
understanding potential drug interactions and their treatment with 200 mg/kg body weight fermented
effects on liver function (Ogbe et al., 2022). Another pawpaw juice resulted in a significant increase in SOD
study by MedlinePlus Drug Information (n.d.) notes that (6.06±0.17), CAT (4.11±0.13), and GSH (5.58±0.38)
NSAIDs, including diclofenac, may cause ulcers, levels. MDA (3.06±0.14) data revealed a significant
bleeding, or holes in the stomach or intestine, decrease in MDA.
emphasizing the potential side effects on the
gastrointestinal tract [2]. Additionally, a report by the The findings suggest that fermented Pawpaw
Food and Drug Administration (FDA) tracks the side juice may offer defense against oxidative stress in the
effects of approved drugs, including diclofenac, and liver and kidney caused by diclofenac.
encourages patients to report any side effects
experienced. Stormer et al., (2022) found that a solitary oral
administration of diclofenac resulted in long-term kidney
damage when there was already a pre-existing

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Arhoghro Ejovwoke Marcellinus et al; SAR J Med Biochem; Vol-5, Iss- 3 (May-Jun, 2024): 22-29.

subclinical acute kidney injury (AKI). According to and water extracts of Carica papaya seed in normal
Stormer et al., (2022), the research discovered that taking and alloxan-induced diabetic rats. Asian Pacific
one dose of diclofenac by mouth led to a shift from an Journal of Tropical Biomedicine, 6(1), 12-16.
experimental, asymptomatic form of acute kidney injury • Alabi, Q. K., & Akomolafe, R. O. (2020). Kolaviron
(AKI) to chronic kidney disease. This underscores the diminishes diclofenac-induced liver and kidney
possible enduring impacts of diclofenac on renal toxicity in wistar rats via suppressing inflammatory
function. Diclofenac also increased the concentrations of events, upregulating antioxidant defenses, and
MDA and H2O2 in the kidneys. MDA is a consequence improving hematological indices. Dose-
of lipid peroxidation, while H2O2 is a byproduct of Response, 18(1), 1559325819899256. doi:
aerobic metabolism (Abiola et al., 2019). These findings 10.1177/1559325819899256. PMID: 32165871;
suggest that diclofenac has the potential to cause PMCID: PMC7054740.
oxidative stress in the kidney, resulting in kidney injury. • Al-Gubory, K. H., Fowler, P. A., & Garrel, C.
To summarize, diclofenac has therapeutic advantages but (2010). The roles of cellular reactive oxygen
also presents significant adverse effects, such as species, oxidative stress and antioxidants in
pulmonary, cardiac, hepatic, and renal tissue damage, as pregnancy outcomes. The international journal of
well as gastrointestinal toxicity (Alabi and Akomolafe, biochemistry & cell biology, 42(10), 1634-1650.
2020). Alabi and Akomolafe's (2020) study suggests that • Anjum, S., Nisar, A., & Mahfooz, S. (2013). Carica
consuming fermented Pawpaw juice could shield the papaya Linn. leaves herbal standardization. Journal
liver and kidney from diclofenac's oxidative stress. of Pharmacognosy and Phytochemistry, 2(2), 6-9.
Diclofenac has the potential to cause long-term damage • Ayo, R. G. (2010). Phytochemical constituent and
to the kidneys in cases where there is already a pre- bioactive of the extract Cassia Nigerians vali: A
existing subclinical acute kidney injury (AKI) (Stormer review. Journal of Medicinal Plants Research,
et al., 2022). Additionally, it can trigger oxidative stress 4(14), 1339-1348.
in the kidneys, resulting in kidney damage. • Benjamin, W. (2020). Anatomy and function of the
liver. Eastern Mediterranean Health Journal, 4(2),
CONCLUSION 350-36
Diclofenac causes kidney and liver damage • Bratner, A., & Grein, E. (1994). Antibacterial
through oxidative damage and hinders immune-mediated Activity of Plant Leaf Extract Used Externally in
defensive mechanisms. Artemisia and Kolaviron are Traditional Medicine. Journal of
potential protective drugs that have demonstrated Ethnopharmacology, 44, 35-40.
hepatoprotective and preventative actions against • Burtis, C., Ashwood, E., Bruns, D., & Tietz, W.
diclofenac-induced damage. Fermented papaya leaf (2008). Tietz Fundamentals of Clinical Chemistry.
extract has the potential to contain antioxidant properties 6th ed. Philadelphia, PA: Saunders; 2008.
that may help protect against hepatorenal impairment. • Chaiamnuay, S., Allison, J. J., & Curtis, J. R. (2006,
October 01). Risks versus benefits of
ACKNOWLEDGMENTS cyclooxygenase-2-selective nonsteroidal anti-
The authors express gratitude to the Technical inflammatory drugs. Am J Health Syst Pharm,
laboratory staff of the Department of Biochemistry at 63(19), 1837-1851.
Niger Delta University, Amassoma. • Dada, F. A., Nzewuji, F. O., Esan, A., Oyeleye, S.,
& Adegbola, V. B. (2016). Phytochemical and
Disclosure of Conflict of Interest: The authors confirm Antioxidant Analysis of Aqueous Extracts of Unripe
that there is no conflict of interest. Pawpaw (Carica Papaya Linn.) Fruit’s Peel and
Seed. International Journal of Research and
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