Aged garlic extract rescues ethephon-induced kidney damage by modulating oxidative stress, apoptosis, inflammation, and histopathological changes in rats

Abstract

Ethephon is an organophosphorus plant growth regulator used to accelerate the ripening process and decrease the duration of cultivation. Here, the potential protective role of aged garlic extract (AGE) was investigated against ethephon-mediated nephrotoxicity. Four experimental groups were established (n = 15), including control, AGE (250mg/kg), ethephon (200mg/kg), and AGE + ethephon. In the current work, kidney function parameters (urea, creatinine, and KIM-1) along with oxidative stress biomarkers, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, glutathione, and its related enzymes, superoxide dismutase, catalase, malondialdehyde, and nitric oxide, were determined. The expression of inflammatory mediators namely tumor necrosis factor alpha, interleukin 1 beta, nuclear factor kappa B, and apoptotic markers (caspase 3, Bax, and Bcl2) were determined in the renal tissue. Additionally, the histopathological alterations in response to treatments were examined. Ethephon exposure increased the levels of kidney function markers along with relative kidney weight coupled with histological changes in the kidney tissue. Additionally, ethephon increased the levels of the tested pro-oxidant markers and decreased the antioxidant indices, resulting in oxidative damage to renal tissues. An elevation in the pro-inflammatory mediators was also recorded following ethephon intoxication. Furthermore, renal cell loss was observed through histological examinations and biochemical measurements upon ethephon administration. On the other hand, AGE significantly ameliorated the molecular, biochemical, and structural changes elicited by ethephon. These findings suggest that AGE may be used to decrease or prevent the side effects of ethephon exposure in kidneys, through the activation of Nrf2 and inhibition of inflammation and apoptotic response.