Zinc normalizes hepatic lipid handling via modulation of ADA/XO/UA pathway and caspase 3 signaling in highly active antiretroviral therapy-treated Wistar rats

Zinc ameliorates acrylamide-induced oxidative stress and apoptosis in testicular cells via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway

“…This study demonstrated that zinc might potentially attenuate acrylamide-induced testicular toxicity, and Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathways may be the target for the gonads-protective strategy of zinc. These results agreed with the study of Ganju and Eastman [ 44 ], Hamed et al [ 18 ], and Akhigbe et al [ 45 ], that reported that zinc suppressed oxidative stress, inflammation, and apoptosis through the modulation of pro-oxidants, antioxidants, pro-inflammatory, apoptotic and antiapoptotic proteins. The gonado-protective effect of zinc is accompanied by the restoration of testicular histoarchitecture and function by preventing degeneration of seminiferous tubules epithelium, loss of sperm cells at the lumen, degeneration of the interstitial cells and normalization of sperm qualities and reproductive hormones.…”

“…The dosage of 1 and 3 mg/kg of elemental zinc used in this study are equal to about 11 and 30 mg/day for humans, which are within the recommended dietary intake of 11 mg and the tolerable upper intake level of 40 mg [ 18 ]. The dosage of acrylamide used in this study is based on the data on occupational exposure to acrylamide in human [ 19 ], and it is similar to the dosage used and reported by Farag et al [ 20 ] and Pourentezari et al [ 21 ].…”

Pathophysiology and management of testicular ischemia/reperfusion injury: Lessons from animal models

“…Hypoxia-induced ROS generation may also be mitochondrial-dependent. Hypoxia induces mitochondrial damage, and activates xanthine oxidase (XO) and inducible nitric oxide synthetase (iNOS) [ 44 ], which are known triggers of oxidative stress [ 45 ]. Mitochondrial damage is associated with reduced mitochondrial oxidative phosphorylation and increased electron leakage from the electron transport chain, leading to increased generation of ROS like superoxide radicals [ 46 ].…”

Gut microbiota-gonadal axis: the impact of gut microbiota on reproductive functions

“…The gut microbiota (microbial-associated molecular patterns, MAMPs, such as lipoprotein acids, lipoproteins, peptidoglycans, and lipopolysaccharide, LPS) translocates into the circulation via the hepatic portal vein or lymphatic system and gets to the testis through the testicular artery to induce hyper-immunological response, chronic inflammation, disruption of blood-testis-barrier, and testicular damage ( 166 ) by activating the innate immune cells and pattern recognition receptors-expressing epithelial cells ( 167 ) through LPS/toll like receptor 4 (TLR4), nuclear factor kappa-B (NFkB)/mitogen-activated protein kinases (MAPK), and MyD88 and TRAM-dependent signaling pathways ( 168 ). The pro-inflammatory cytokines also activate xanthine oxidase, leading to increased generation of uric acid and oxidative stress ( 169 – 171 ) that causes Leydig and Sertoli cells damage ( 172 – 174 ). In addition, accumulation of macrophages and dendritic cells in the epididymal lumen may trap normal sperm cells and trigger immunological damage ( 175 ).…”