Abstract
BackgroundDillenia indica fruit is known for its numerous health benefits in folk medicine including its use to cure kidney diseases. The present study was designed to investigate the protective effect of D. indica fruit extracts on cisplatin-induced nephrotoxicity.MethodsA nephrotoxic dose of cisplatin (3 mg/kg b.w./day, i.p) was administered every fifth day to the animals receiving vehicle or fruit extracts (methanol, ethyl acetate, and petroleum ether) daily for 25 days. Rats were sacrificed on the 25th day, and the effect of extracts was assessed by determining the alterations in various serum and urine parameters, membrane-bound enzyme, and antioxidant defense system in kidney tissue.ResultsIncrease in serum urea, uric acid, creatinine, blood urea nitrogen, phospholipid, and cholesterol and a decrease in urine urea, uric acid, creatinine, and creatinine clearance rate were reported in the cisplatin control group. Cisplatin alters electrolyte balance, brush border membrane marker enzyme (i.e., alkaline phosphatase, γ-glutamyl transferase, leucine aminopeptidase) activity, and redox balance significantly. Methanol and ethyl acetate extracts of D. indica fruit produced beneficial effect and ameliorated serum and urine parameter to normal. Extract administration increases Na+/K+-ATPase activity and different enzymatic and non-enzymatic antioxidants positively, whereas lipid peroxidation reduced significantly. Extracts exhibited a potent in vitro antioxidant activity.ConclusionTaking into account these results, it can be assumed that D. indica fruit could be the future key candidate which may maximize the clinical use of cisplatin in the treatment of different cancer without nephrotoxicity.
Highlights
Dillenia indica fruit is known for its numerous health benefits in folk medicine including its use to cure kidney diseases
Considering OECD guideline, 2000 mg/kg dose was categorized under Globally Harmonized Classification System (GHS) category 5, as per OECD guideline 423 (Annexure 2d)
The IC50 values of DIEE (15.8 ± 0.02 μg/ml) and DIME (29.3 ± 0.03 μg/ml) against DPPH were observed while IC50 values of DIME (28.22 ± 0.34 μg/ml) and DIEE (34.0 ± 0.55 μg/ml) against Nitric oxide (NO) and the IC50 values of DIME (61.5 ± 0.60 μg/ml) and DIEE (70.7 ± 0.54 μg/ml) against lipid peroxidation inhibition assay (Table 1)
Summary
Dillenia indica fruit is known for its numerous health benefits in folk medicine including its use to cure kidney diseases. The present study was designed to investigate the protective effect of D. indica fruit extracts on cisplatin-induced nephrotoxicity. The incidence of drug-induced nephrotoxicity has been increasing at a frightening rate with the increasing uses of antibiotics and anticancer drugs [1]. Oxidative stress is considered as a key factor for drug-induced nephrotoxicity [2]. Cisplatin [cis-diamminedichloroplatinum (II)] is the most common and potent anticancer drug used against a diverse spectrum of malignancies. (Family: Dilleniaceae) is a wildly available medicinal plant found in Northeast India. The common name of the plant is outenga in Assamese and chalita in Bengali. The fruits and other parts of the plant are used traditionally to cure a number of ailments like stomach
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