Silver nanoparticles induced testicular damage targeting NQO1 and APE1 dysregulation, apoptosis via Bax/Bcl-2 pathway, fibrosis via TGF-β/α-SMA upregulation in rats

Abstract

In medicine, silver nanoparticles (AgNPs) are employed often. They do, however, have negative impacts, particularly on the reproductive organs. This research aimed to assess AgNP impact on the testis and the possible intracellular mechanisms to induce testicular deteriorations in rats at various concentrations and different time intervals. Sprague Dawley rats (n = 40) were allocated into four equal groups: the control one, and three other groups injected intra-peritoneally with AgNP solution 0.25, 0.5, and 1 mg/kg b.w. respectively for 15 and 30 days. Our findings revealed that AgNPs reduced body and testicular weights, estradiol (E2) and testosterone (T) hormone levels, and sperm parameters while elevating the nitric oxide and malondialdehyde levels with inhibition of reduced glutathione contents in testicular tissue. Interestingly, AgNPs significantly upregulated the testicular inducible nitric oxide synthase, B cell lymphoma 2 (Bcl-2)-associated X, transforming growth factor, and alpha-smooth muscle actin (α-SMA) expression levels. However, apurinic/apyrimidinic endo deoxyribonuclease 1 (APE1), NAD (P) H quinone dehydrogenase 1 (NQO1), and Bcl-2 expression levels were all downregulated indicating exhaustion of body antioxidant and repairing defense mechanisms in testicles in comparison with the control rats. Various histological alterations were also detected which dramatically increased in rats sacrificed after 30 days such as loss of the lining cells of seminiferous tubules with no spermatozoa and tubular irregularities associated with thickening of their basement membranes. Immunolabeling implicated in the apoptotic pathway revealed a negative expression of Bcl-2 and marked immunoreactivity for caspase-3 after 30 days of AgNP treatment in comparison to the control rats. To our knowledge, there have been no previous publications on the role of the α-SMA, APE1, and NQO1 genes in the molecular pathogenesis of AgNP testicular cytotoxicity following AgNP acute and chronic exposure. Graphical Abstract

Exogenous taurine administration abates reproductive dysfunction in male rats exposed to silver nanoparticles

“…The increase NO level, MPO activity, and TNF‐α level observed in the AgNPs‐exposed rats in the current research suggests induction of inflammatory stress in the investigated tissues. Our current finding on cellular inflammatory response associated with AgNPs exposure is consistent with earlier studies 20,23 . Furthermore, activated cysteine‐aspartic protease known as caspase‐3 which executes apoptotic cell death following specific cleavage of cellular proteins was markedly increased following AgNPs treatment, thus indicating induction of apoptotic response in the hypothalamic, testicular and epididymal tissues.…”

“…Our current finding on cellular inflammatory response associated with AgNPs exposure is consistent with earlier studies. 20,23 Furthermore, activated cysteine-aspartic protease known as caspase-3 which executes apoptotic cell death following specific cleavage of cellular proteins was markedly increased following AgNPs treatment, thus indicating induction of apoptotic response in the hypothalamic, testicular and epididymal tissues. The marked abatement in the MPO activity, NO and TNF-α levels as well as caspase 3 activity in tissues of AgNPs-treated rats by exogenous administration of taurine indicates chemoprotection via anti-inflammatory and anti-apoptotic activities in the treated animals.…”

“…Moreover, single injection of 5 and 10 mg/kg body weight of AgNPs (20 and 200 nm sizes) for 24 h, 7 and 28 days caused a time‐ and dose‐dependent decrease in the epididymal sperm count with elevated abnormal sperm and DNA damage in germ cells in rats 18 . Repeated intra‐peritoneal injection of rats with AgNPs reportedly suppressed reproductive hormones, 19 induced oxidative injury to Leydig cells, Sertoli cells, seminiferous tubules and sperm chromatin integrity 20–22 as well as triggered inflammation and apoptosis in testes of rats 20,23 . Owing to the adverse effects of AgNPs on reproductive system, there is need for therapeutic strategies to abrogate this toxicity.…”

“…18 Repeated intra-peritoneal injection of rats with AgNPs reportedly suppressed reproductive hormones, 19 induced oxidative injury to Leydig cells, Sertoli cells, seminiferous tubules and sperm chromatin integrity [20][21][22] as well as triggered inflammation and apoptosis in testes of rats. 20,23 Owing to the adverse effects of AgNPs on reproductive system, there is need for therapeutic strategies to abrogate this toxicity. Thus, natural bioactive compounds with potent antioxidant, anti-peroxidative, anti-inflammatory and anti-apoptotic activities will serve as good antidotes to AgNPs-induced toxicity.…”

Alleviative Role of Hemin on Reproductive Functions of Adult Male Rats Treated with Copper Oxide Nanoparticles

“…These findings support the suggestions made by Al-Bairuty and Taha (2016) and De Jong et al (2019) that this type of exposure may be actually harmful. The cause of the animal's declining average body weight might be a biological alteration that influences the animal's appetite and feed intake, or it could be the disruption of several metabolic activities brought on by oral gavage (Assar et al, 2023). However, in recent studies performed by Ouni et al (2020) and Bugata et al (2019), it was found that daily oral administration of CuO NPs did not impact the feed intake and the weight of the body.…”