Ziziphus spina-christi Leaf Extract Suppressed Mercury Chloride-Induced Nephrotoxicity via Nrf2-Antioxidant Pathway Activation and Inhibition of Inflammatory and Apoptotic Signaling

Exposure to heavy metals, including mercury chloride (HgCl(2)), is associated with severe health problems. This study was designed to investigate HgCl(2)-induced nephrotoxicity and evaluate the protective role of Ziziphus spina-christi leaf extract (ZSCLE). Four randomly selected groups containing seven rats were used. For a period of 28 days, the control group was administered 0.9% saline solution; the second group was administered 300 mg/kg ZSCLE; the third group was administered 0.4 mg/kg HgCl(2) dissolved in 0.9% physiological saline solution; and the fourth group was administered an oral supplement of 300 mg/kg ZSCLE one hour after HgCl(2) administration. HgCl(2) intoxication resulted in Hg accumulation in renal tissue; decreases in body weight, kidney index, and glutathione content and superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities; increases in creatinine, urea, Kim-1 expression, lipid peroxidation, and nitric oxide production; suppression of the Nrf2-antioxidant response pathway; upregulation of Il1β, Tnfα, and Nos2; and potentiation of proapoptotic activity. ZSCLE exerted beneficial effects against mercury-induced renal toxicity and significantly reversed these alterations to near normal values. These effects resulted from its chelation and antioxidant, anti-inflammatory, and antiapoptotic activities. ZSCLE may prevent or minimize the pathological changes induced by mercury in the kidney.