Zero Hunger (SDG 2), Good Health & Well-being (SDG 3)
Unraveling the path toward in search of nephroprotective drug leads from Sri Lankan flora Kottawa Gamage Anoja Priyadarshani Attanayake* Department of Biochemistry, Faculty of Medicine, University of Ruhuna, Sri Lanka The multifactorial nature of drug-induced nephrotoxicity often requires therapeutic approaches with diverse protective effects at target sites. Doxorubicin is an anthracycline drug in which use in cancer chemotherapy has been largely limited due to its dose-dependent nephrotoxicity. The revival of interest in the use of medicinal plants as nephroprotective agents has emerged worldwide as sources of new drug leads aimed at the management of drug-induced nephrotoxicity. The present study was to investigate the nephroprotective effects of selected medicinal plant extracts of Sri Lankan origin in an animal model of doxorubicin-induced nephrotoxicity and to assess their safety in healthy Wistar rats. Efficacy of aqueous refluxed (4h) extracts of Abelmoschus moschatus Medikus. (leaves), Asparagus falcatus L. (leaves), and Barleria prionitis L. (whole plant) at three selected doses were investigated for nephroprotective activity in rats with doxorubicin (20 mg/kg, ip) induced nephrotoxicity. Post-treatment with the selected plant extracts for three consecutive days resulted in significant dose-dependent nephroprotective effects in experimental rats (p<0.05). Based on the success of the screening, the three plants were subjected to investigate on the assessment of toxicity effects and detailed nephroprotective mechanisms in vivo. Repeated 28-day dose oral toxicity effects of hexane, ethyl acetate, butanol, and aqueous extracts of A. moschatus (55, 75, 60, 140 mg/kg), A. falcatus (55, 35, 75, 200 mg/kg), and B. prionitis (25, 80, 70, 120 mg/kg) for 28 days were evaluated in healthy Wistar rats following OECD guidelines. No toxicological effects were observed on kidney and liver function tests, hematological parameters, and histopathology of the body organs in healthy male and female Wistar rats after administration of the selected extracts at the equivalent therapeutic doses. In detailed investigations on nephroprotective mechanisms, the selected plant extracts at therapeutic doses showed significant nephroprotective effects against acute nephrotoxicity in Wistar rats by reducing serum concentrations of creatinine, blood urea nitrogen, β2-microglobulin, and urine total protein levels (p<0.05). Treatment with the selected medicinal plant extracts for 28 consecutive days resulted in a suppression of both TNF-α and IL-1β compared to that in rats of the doxorubicin control group (p<0.05). The selected medicinal plant extracts were found to attenuate doxorubicin-induced oxidative stress by restoration of antioxidant status, as shown by increased values of total antioxidant status and glutathione reductase and glutathione peroxidase activities and a reduction in lipid peroxidation in the treated groups. The biochemical results were further corroborated by histopathological observations, which demonstrated significant nephroprotective effects, with reference to attenuation of tubular and glomerular changes in the kidney tissues of the treated rats. Further, the immunohistochemical expression of the pro-apoptotic, Bax protein was decreased and the expression of the anti-apoptotic, BCL-2 was increased following the treatments. In conclusion, the findings revealed that the selected plant extracts counteract nephrotoxicity induced by doxorubicin via antioxidant, anti-inflammatory, and anti-apoptotic pathways. The present findings would open future research avenues for the isolation of pharmacologically active compounds for designing potential antidotes to minimize doxorubicin-induced nephrotoxicity in patients with cancers.
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© The Author(s), 2023
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