Bisphenol A (BPA), an organic synthetic compound and endocrine disruptor, which majorly cause deleterious effects on male reproductory system. Fenugreek (Trigonella foenum-graecum), associated with Leguminosae family is used as a herbal medicine with potent antioxidant properties. The present study was aimed to scrutinise the preventative role of fenugreek seeds aqueous extract (FSEt) on BPA-induced testicular damage in mice. Study included four different groups of male Balb/c mice: contol (C), fenugreek (FSEt), bisphenol A (BPA) and fenugreek + bisphenol A (FSEt + BPA).After two months of treatment, assessment of sperm parameters, antioxidant defence system, histopathological studies, germ cell count and gene expression of intrinsic apoptotic pathway were carried out. Administration of FSEt improved the damage caused by BPA as indicated by improved sperm parameters. FSEt-administered mice showed improvement in the histoarchitecture compared with BPA-administered animals. In addition, fenugreek treatment showed reduced levels of malondialdehyde and elevated levels of antioxidant enzymes. Expression studies of apoptotic markers revealed a significant decrease in the expression of Bcl-2 and significant increase in caspase-9 and caspase-3. However, FSEt restored the deleterious effects caused by BPA. The current findings plausibly might have promising protective role against BPA-induced testicular damage. K E Y W O R D Santioxidants, apoptosis, bisphenol A, fenugreek, oxidative stress

Bisphenol A (BPA) is a well‐known endocrine disruptor that imposees adverse effects on male fertility via interacting with germ cells of testis. Objectives of present study were to investigate the possible protective effects of hydroethanolic Murraya koenigii leaves extract (HEMKLE) against BPA‐induced testicular damage and apoptosis in mice. Male Balb/c mice were divided into four different groups: Group I (control), Group II (HEMKLE), Group III (BPA) and Group IV (HEMKLE + BPA). Group III (BPA) showed significant decrease in sperm parameters, germ cell number along with increased lipid peroxidation (LPO) and reactive oxygen species (ROS). A significant decrease in antioxidant enzymes activity was also observed in Group III (BPA) animals. mRNA expression study revealed significant decrease in the expression of Bcl‐2 and increase in expressions of caspase‐9 and caspase‐3, thus clearly demonstrate BPA‐induced apoptosis. In addition, HEMKLE co‐administration to BPA‐treated mice showed a significant increase in sperm parameters, germ cell number, decreased levels of LPO and ROS, increased antioxidant enzymes activity in Group IV (HEMKLE + BPA). Also, mRNA expression study showed a significant increase in Bcl‐2 and decrease in caspase‐9 and caspase‐3 gene expressions in Group IV (HEMKLE + BPA). Thus, the present study suggests that HEMKLE intervention provides protection against BPA‐induced oxidative stress and apoptosis.

Being a vital micronutrient, along with a trace element, selenium (Se) protects the cells from oxidative stress (OS) in the form of selenoproteins. Bisphenol A (BPA) is a xeno‐oestrogenic compound that adversely affects the spermatogenesis process by inducing oxidative stress, which ultimately leads to male infertility. Therefore, it is hypothesised that Se could protect against BPA‐induced OS, and further germ cell death by modifying mitogen‐activated protein kinase (MAPK) signalling. Male Balb/c mice were divided into four groups: Group I (C) (0.2 ppm Se), Group II (Se) (0.5 ppm Se), Group III (BPA) (0.2 ppm Se, and BPA = 1 mg/kg orally) and Group IV (Se + BPA) (0.5 ppm Se, and BPA = 1 mg/kg bodyweight orally). Results indicated that BPA‐treated animals demonstrated a marked decrease in antioxidant enzyme activities (superoxide dismutase, catalase, redox ratio), a marked elevation in the expressions of stress‐activated kinases (c‐Jun NH2‐terminal kinase (JNK), extracellular signal‐regulated kinase (ERK) and p38) and the expressions of pro‐apoptotic markers (caspase‐9, caspase‐8 and caspase‐3). However, Se supplementation considerably restored the antioxidant enzyme activities and lowered the expressions of stress‐activated kinases, which further down‐regulated the apoptosis. Thus, Se supplementation demonstrated to be effective against BPA provoked testicular damage.

Doxorubicin, a chemotherapeutic drug, is known to disrupt the normal spermatogenesis by excess oxidative stress. The present study describes the curative effects of dietary supplemented selenium on doxorubicin‐induced testicular damage in mice. Four groups were included in the study: Group I(C), Group II (Se‐0.5 ppm/kg diet), Group III (Dox‐3mg/kg body weight i.p.) and Group IV (Se + Dox). We analysed microscopic sperm parameters, histopathology, testicular germ cell kinetics, oxidative stress levels, antioxidant levels and mRNA expression studies of apoptotic and stress response markers. Sperm parameters were significantly reduced in doxorubicin‐treated group. Moreover, mice treated with doxorubicin showed an elevation in oxidative stress markers as well as decreased redox ratio, and antioxidant levels were observed in Group III (Dox). However, selenium supplementation ameliorated the damage incurred by doxorubicin, by improving sperm parameters, antioxidant levels and histoarchitecture of mice testes, and decreased the oxidative stress levels. Selenium administration also reduced the levels of apoptotic caspases and stress‐activated kinases in Group IV (Se + Dox) when compared to Group III (Dox). In conclusion, selenium exhibits the curative effect against doxorubicin‐induced testicular damage in mice by attenuating stress conditions and associated apoptosis.

A review on the pathogenesis of cutaneous non-melanoma skin cancer (NMSC) and selected herbs as chemoprotective agents.