Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk

Abstract

Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has a great ability to stimulate antioxidant processes. This study aimed to investigate the possible mitigating effect of ZW on CsA-induced nephrotoxicity and its underlying mechanisms. Forty rats were allocated into four groups (n = 10): a control group, ZW group, cyclosporine A group (injected subcutaneously (SC) with CsA (20 mg/kg/day)), and cyclosporine A+ Zamzam water group (administered CsA (SC) and ZW as their only drinking water (100 mL/cage/day) for 21 days). Exposure to CsA significantly (p < 0.001) increased the serum creatinine level, lipid peroxidation marker level (malondialdehyde; MDA), and the expression of apoptotic markers procaspase-8, caspase-8, caspase- 9, calpain, cytochrome c, caspas-3, P62, and mTOR in renal tissues. Meanwhile, it markedly decreased (p< 0.001) the autophagic markers (AMPK, ULK-I, ATag5, LC3, and Beclin-1), antiapoptotic Bcl-2, and antioxidant enzymes. Moreover, the administration of CsA caused histological alterations in renal tissues. ZW significantly (p < 0.001) reversed all the changes caused by CsA and conclusively achieved a positive outcome in restraining CsA-induced nephrotoxicity, as indicated by the restoration of the histological architecture, improvement of renal function, inhibition of apoptosis, and enhancement of autophagy via the AMPK/mTOR pathway.

Investigation of antimicrobial and antioxidant activities of Chenopodium album extracts and their effects on gentamicin nephrotoxicity in rats

“…Lipid peroxidation leads to the breakdown of cellular membranes and subsequent shedding of the contents of the cytoplasm into the tubular lumen and can account for the appearance of hyaline casts (Taha et al, 2023 ).…”

Alkaline Water Mitigates Bone Loss in Streptozotocin-Induced Type II Diabetic Rats

“…On the contrary, diabetic rats receiving ZW significantly increased osteoblastic markers (OC and ALP), while at the same time decreasing bone resorption markers (TRAP-5b, NTX-1, and DPD), with clear improvement in the X-ray image of the L6 lumbar vertebra level. This can be regarded as the physical and chemical characteristics of ZW due to its alkaline composition and its high concentration of trace elements, such as magnesium (520 mg/L) and calcium (189 mg/L), in comparison to tap water, which contributes to bone density, as well as its powerful antioxidant character by elevating antioxidant enzymes [ 38 ]. Oxidative stress markedly inhibits osteoblast differentiation and activation [ 39 ].…”