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

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RESEARCH ARTICLE

Aged garlic extract rescues ethephon-induced kidney damage by modulating oxidative stress, apoptosis, inflammation, and histopathological changes in rats Ashraf Albrakati 1 Received: 1 June 2020 / Accepted: 25 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

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 (250 mg/kg), ethephon (200 mg/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. Keywords Ethephon . Aged garlic extract . Kidney . Oxidative stress . Inflammation . Apoptosis

Introduction Plant growth regulators are agrochemical compounds that increase crop productivity, and their excessive application is associated with several adverse health effects (Hodjat et al. 2017). Ethephon (2-chloroethylphosphonic acid) is an organophosphorus insecticide widely used to accelerate the ripening process and decrease the cultivation duration. Ethephon catabolizes into ethylene oxide, thereby yielding ethanediol,

Responsible Editor: Mohamed M. Abdel-Daim * Ashraf Albrakati [email protected] 1

Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia

hydroxyethyl-glutathione, and mercapturic acid (Bhadoria et al. 2018a). Ethephon toxicity may result from the consumption of artificially ripened crops (Bh