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ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 4  |  Page : 245-249

Effects of Zingiber officinale Aqueous Leaf Extract on Vincristine-Induced Kidney Damage in Adult Wistar Rats


Department of Anatomy, University of Benin, Benin City, Edo, Nigeria

Date of Submission23-Aug-2021
Date of Decision31-Aug-2021
Date of Acceptance31-Aug-2021
Date of Web Publication19-May-2022

Correspondence Address:
Dr. Richard O Agbonluai Ehimigbai
Department of Anatomy, University of Benin, Benin City, Edo
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njecp.njecp_35_21

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  Abstract 


Background: Vincristine, although used as a chemotherapy drug, has been reported to induce nephrotoxicity, while Zingiber officinale, a medicinal plant, possesses antioxidant, antiapoptotic, and antitumorigenic properties. Aim and Objectives: In this study, we examined the effects of Z. officinale against vincristine-induced kidney damage by analyzing renal function, enzymatic antioxidants, and renal tissue. Materials and Methods: Thirty adult Wistar rats, weighing between 140 g and 185 g, were assigned into six groups of five animals each. Groups A, B, C, D, E, and F received 1 ml of distilled water, 200 mg/kg of Z. officinale aqueous extract, 1000 mg/kg of Z. officinale aqueous extract, 50 μg/kg of vincristine only, 200 mg/kg of Z. officinale aqueous extract and 50 μg/kg of vincristine, and 1000 mg/kg of Z. officinale aqueous extract and 50 μg/kg of vincristine, respectively. Administration of vincristine was by a 10-day intraperitoneal injection, while that of Z. officinale was by gavage, for a period of 28 days. Food and water were provided across all groups, ad libitum. Results: Vincristine significantly (P < 0.05) increased the levels of creatinine, urea, chloride, and malondialdehyde while having a reducing effect on the levels of superoxide dismutase and catalase. The histology revealed that vincristine caused a distortion of the renal architecture. Conclusion: The administration of Z. officinale mitigated the aforementioned debilitating effects of vincristine.

Keywords: Nephrotoxicity, vincristine, Wistar rats, Zingiber officinale


How to cite this article:
Ehimigbai RO, Akpobaro AE. Effects of Zingiber officinale Aqueous Leaf Extract on Vincristine-Induced Kidney Damage in Adult Wistar Rats. Niger J Exp Clin Biosci 2021;9:245-9

How to cite this URL:
Ehimigbai RO, Akpobaro AE. Effects of Zingiber officinale Aqueous Leaf Extract on Vincristine-Induced Kidney Damage in Adult Wistar Rats. Niger J Exp Clin Biosci [serial online] 2021 [cited 2022 Jul 1];9:245-9. Available from: https://www.njecbonline.org/text.asp?2021/9/4/245/345554




  Introduction Top


According to the World Health Organization's global health estimates, cancers impose the largest worldwide burden both in men and in women.[1] Cancer has been one of the leading causes of death ravaging the globe due to its lethal mechanism of growth and attack on human cells. Chemotherapy is one of the most common modalities used in the treatment of cancer patients. However, many established chemotherapy drugs are antiproliferative agents, targeting rapidly dividing cancer cells but also indiscriminately damaging nonmalignant dividing cells, leading to various organ toxicities.[2]

In fact, drug-induced nephrotoxicity is a major cause of acute kidney injury, being responsible for quite a number of hospital admissions. Drug-induced kidney disease is recognized as the main cause of mortality and morbidity.[3],[4] One of such drugs implicated in causing damage to the kidney is vincristine.[2] In the treatment of cancer types such as sarcomas, lymphomas, and leukemias, vincristine has proven to be quite efficient, as evident from its routine use.[5] Vincristine is a plant-based drug, possessing antineoplastic properties which aid the management of several cancerous conditions.[6],[7]

Cytotoxicity caused by vincristine is facilitated chiefly through inducing apoptosis[8] and to a lesser degree, inducing necrosis.[9] Research has shown that the apoptosis induced by vincristine is due to induction of oxidative stress and inflammation,[10] inhibition of manufacture of nucleic acids and proteins,[11] arrest of cell cycle division during the metaphase,[12] and disruption of microtubules.[7],[8]

Tissues have a high binding capacity to vincristine, and this leads to a build of vincristine in them, excluding the eyes, brain, and fatty tissues.[13],[14] Moreover, the kidney is a metabolic organ which oxidizes drugs through cytochrome p450 and other enzyme systems, situated within the renal parenchyma, into different metabolites. Some of these metabolites end up damaging the kidneys through a number of mechanisms, including, but not limited to oxidative stress and the formation of injurious reactive oxygen species.[15]

Nephropathies linked with chemotherapeutic drugs include tubulointerstitial damage[16] and glomerular disease.[17] Hardly surprising, as kidneys are one of the most highly vulnerable organs in the body to drug-induced toxicity due to the high blood supply they receive (25% of cardiac output), their significant capacity to uptake drugs via endocytosis or transporter proteins, and their crucial role in the metabolism, excretion, and elimination of toxic agents and their metabolites.[18],[19],[20]

Medicinal plants are known to play important functions in traditional health-care systems for the management of several medical conditions. Their medicinal value is enshrined in their phytochemical component which produces certain physiological actions. Zingiber officinale is an important plant with several medicinal, ethnomedicinal, and nutritional values.[21] It is the underground rhizome of the ginger plant which possesses a firm, striated texture. Z. officinale, commonly known as ginger, belongs to the family Zingiberaceae.[22]

Its cultivation is said to have originated in China and eventually spreads to India, South East Asia, West Africa, and the Caribbean.[23] Z. officinale has been reported to demonstrate high antioxidant,[24] antiapoptotic activity,[25] and renoprotective activities.[26] In this study, we examined the effects of Z. officinale against vincristine-induced kidney damage by analyzing renal function, enzymatic antioxidants, and renal tissue.


  Materials and Methods Top


Plant materials

Z. officinale was collected in a farm at Oluku, in Ovia North East Local Government Area of Edo State, Nigeria. The leaves were identified and authenticated in the Department of Plant Biology and Biotechnology, Faculty of Life Sciences, University of Benin, Benin City, where they were assigned Herbarium Number UBH-Z384. The result of phytochemical screening of aqueous extract of Z. officinale revealed the presence of alkaloids, flavonoids, saponins, tannins, and phenols.[27]

Animals

Thirty adult Wistar rats, weighing between 140 g and 185 g, were assigned into six groups of five animals each (as shown in [Table 1]). The animals were purchased from the Animal House of the Department of Anatomy, University of Benin, Benin City, Edo state. The experimental protocols were carried out to conform to the acceptable guidelines on the ethical and humane use of animals in research.[28]
Table 1: Groups and administered dosage

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Chemicals

Vincristine sulfate (Chandra Bhagat Pharma Pvt. Ltd., Mumbai) was dissolved in normal saline. All the reagents used in the present study were of analytical grade.

Experimental design

Administration of vincristine was by a 10-day intraperitoneal injection, while that of Z. officinale was by gavage, for a period of 28 days. Food and water were provided across all groups, ad libitum.

Sample collection

After 28 days of administration, the experimental rats were sacrificed via chloroform anesthesia method. Blood samples were collected in plain bottles for biochemical assays. The renal tissues were harvested, weighed, and promptly fixed.

Histopathology

The renal tissues were excised and stored in labeled bottles containing buffered formal saline, for tissue processing. After fixation, they were dehydrated in the ascending grades of alcohol, cleared in xylene, and embedded in paraffin wax. The deparaffinized sections were stained routinely with hematoxylin and eosin.[29] Photomicrographic plates of the desired sections were taken, using a standard photomicrography setup, namely Olympus XSZ-107BN microscope and an attached Eakins 1080P microscopic camera.

Statistical analyses

Data were subjected to statistical analysis using the IBM SPSS statistics software Statistical Package for Social Science Version 25, (New York, United States of America) and relevant statistical values were obtained. One-way analysis of variance was carried out and data were presented as mean ± standard deviation of the error. LSD post-hoc test was used. Values of P < 0.05 were considered significant. The statistical values obtained were converted into tabless.


  Results Top


Results from the analysis of renal function tests showed that a high dose of Z. officinale aqueous leaf extracts significantly (P < 0.05) increased the levels of potassium and significantly (P < 0.05) decreased the levels of chloride. Low dose of Z. officinale aqueous leaf extract also significantly (P < 0.05) decreased the levels of chloride. The administration of vincristine caused a significant (P < 0.05) increase in the levels of chloride, creatinine, and urea, while Z. officinale in low and high doses reversed the increases.

Results from the analysis of the enzymatic antioxidants showed that the administration of vincristine significantly (P < 0.05) increased the levels of malondialdehyde, while it also significantly (P < 0.05) reduced the levels of superoxide dismutase and catalase. The animals that received low and high doses of Z. officinale showed a reversal – to levels comparable with the control group – of vincristine-induced activities.

The photomicrograph of the control group [Plate 1] shows the normal architecture of the kidneys. In Group B [Plate 2], which received a low dose of Z. officinale, normal histological features were also observed, and in Group C [Plate 3], similar normal features were seen. However, in Group D [Plate 4] distortions of the renal architecture, in the form of extravasation of erythrocytes into the interstitial spaces, dilated and congested blood vessels were observed, while in Groups E and F [Plate 5] and [Plate 6], respectively), the aforementioned irregularities were upturned.


  Discussion Top


Although vincristine is efficacious as an anticancer drug, it is also known to be nephropathic. The frequency of nephrotoxicity caused by drugs[30],[31] and adverse drug reactions has been recorded in several instances.[18],[32] Glomerular histopathological distortions and renal function tests are considered to be veritable tests of kidney function in animals.[33] It has been long established that high serum creatinine and urea levels are key nephropathic markers.[34] This is because when creatine is metabolized in the muscles, it produces creatinine which is seamlessly filtered.[34] As a result, it is only when renal function is severely impaired that serum creatinine levels are elevated significantly.[35]

In addition, the significant increase in creatinine and urea has been linked with distinct renal structural damage.[36] In our study, we recorded statistically significant increases of serum urea and creatinine levels after the administration of vincristine which corroborates (as shown in [Table 2]) vincristine's nephrotoxic properties that have been reported in previous studies. However, the administration of Z. officinale reduced the previously elevated levels of creatinine and urea to levels comparable with the control group. This is a testament to Z. officinale's renotherapeutic abilities as previously reported.[37],[38]
Table 2: Effect of Zingiber officinale and vincristine on renal function test parameters

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This study also investigated the effects of aqueous leaf extract of Z. officinale and vincristine on enzymatic antioxidants (malondialdehyde, superoxide dismutase, and catalase). According to researchers,[39] malondialdehyde estimates are a good measure of lipid peroxidation. We discovered that the 10-day administration of vincristine significantly increased the mean values of malondialdehyde levels in vincristine-exposed rats. This is harmonious with results from investigators,[40] who reported a similar finding after vincristine exposure in their experimental animals.

It is typical to record a significant stress-induced decline in the activities of superoxide dismutase and catalase levels following vincristine treatment.[41] These reports are consistent with our findings after vincristine treatment [Table 3]. On the other hand, the supplementation with Z. officinale increased the previously depleted levels of superoxide dismutase and catalase [Table 3]. Our results are in a good agreement with previous studies, as scholars[42] reported that Z. officinale increases antioxidant levels. These results may be attributed to the antioxidant effect of Z. officinale[43] and its ability to maintain the cell membrane integrity[44] which are associated with its active ingredients such as gingerols and shogaols which are considered to be very important components.[45]
Table 3: Effect of Zingiber officinale and vincristine on antioxidants assay

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There are reports of nephrotoxic drugs resulting in damage to the renal tubules and glomerulus while also causing interstitial inflammation.[11],[12] We recorded similar findings after the initial assault with vincristine (as shown in [Plate 4]). However, treatment with Z. officinale induced improvement in histopathological structures of the kidneys in the experimental rats Supplementary 1.


  Conclusion Top


Results from this study demonstrated that aqueous leaf extract of Z. officinale ameliorated vincristine-induced kidney damage.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.


  Supplementary 1 Top
















 
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    Tables

  [Table 1], [Table 2], [Table 3]



 

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