α-lipoic acid protects testis and epididymis against linuron-induced oxidative toxicity in adult rats.

Linuron is well known for its antiandrogenic property. However, the effects of linuron on testicular and epididymal pro- and antioxidant status are not well defined. On the other hand, α-lipoic acid is well known as universal antioxidant. Therefore, the purpose of this study was twofold: firstly to investigate whether linuron exposure alters antioxidant status in the testis and epididymis of rats and if so, whether the supplementation of α-lipoic acid mitigates linuron-induced oxidative toxicity in rats. To address this question, α-lipoic acid at a dose of 70 mg/Kg body weight (three times a week) was administered to linuron exposed rats (10 or 50 mg/Kg body weight, every alternate day over a period of 60 days), and the selected reproductive endpoints were analyzed after 60 days. Respective controls were maintained in parallel. Linuron at selected doses reduced testicular daily sperm count, and epididymal sperm count, sperm motility, sperm viability, and number of tail coiled sperm, reduced activity levels of 3ß- and 17ß-hydroxysteroid dehydrogenases, decreased expression levels of StAR mRNA, inhibition of testosterone levels, and elevated levels of testicular cholesterol in rats over controls. Linuron intoxication deteriorated the structural integrity of testis and epididymis associated with reduced the reproductive performance over controls. Conversely, α-lipoic acid supplementation enhanced sperm quality and improved the testosterone synthesis pathway in linuron exposed rats over its respective control. Administration of α-lipoic acid restored inhibition of testicular and epididymal enzymatic (superoxide dismutase, catalase, glutathione reductase, glutathione peroxidise) and non-enzymatic (glutathione content), increased lipid peroxidation and protein carbonyl content produced by linuron in rats. α-lipoic acid supplementation inhibited the expression levels of testicular caspase-3 mRNA levels and also its activity in linuron treated rats. To summate, α-lipoic acid-induced protection of reproductive health in linuron treated rats could be attributed to its antioxidant, and steroidogenic properties.

Phenotypic and transcriptomic changes in zebrafish (Danio rerio) embryos/larvae following cypermethrin exposure.

Cypermethrin is one of the widely used type-II pyrethroid and the indiscriminate use of this pesticide leads to life threatening effects and in particular showed developmental effects in sensitive populations such as children and pregnant woman. However, the molecular mechanisms underlying cypermethrin-induced development toxicity is not well defined. To address this gap, the present study was designed to investigate the phenotypic and transcriptomic (next generation RNA-Seq method) impact of cypermethrin in zebrafish embryos as a model system. Zebrafish embryos at two time points, 24 h postfertilization (hpf) and 48 hpf were exposed to cypermethrin at a concentration of 10 µg/L. Respective control groups were maintained. Cypermethrin induced both phenotypic and transcriptomic changes in zebrafish embryos at 48 hpf. The phenotypic anomalies such as delayed hatching rate, increased heartbeat rate and deformed axial spinal curvature in cypermethrin exposed zebrafish embryos at 48 hpf as compared to its respective controls. Transcriptomic analysis indicated that cypermethrin exposure altered genes associated with visual/eye development and gene functional profiling also revealed that cypermethrin stress over a period of 48 h disrupts phototransduction pathway in zebrafish embryos. Interestingly, cypermethrin exposure resulted in up regulation of only one gene, tnnt3b, fast muscle troponin isoform 3T in 24 hpf embryos as compared to its respective controls. The present model system, cypermethrin exposed zebrafish embryos elaborates the toxic consequences of cypermethrin exposure during developmental stages, especially in fishes. The present findings paves a way to understand the visual impairment in sensitive populations such as children exposed to cypermethrin during their embryonic period and further research is warranted.

α-lipoic acid inhibits oxidative stress in testis and attenuates testicular toxicity in rats exposed to carbimazole during embryonic period.

The aim of this study was to evaluate the probable protective effect of α-lipoic acid against testicular toxicity in rats exposed to carbimazole during the embryonic period. Time-mated pregnant rats were exposed to carbimazole from the embryonic days 9-21. After completion of the gestation period, all the rats were allowed to deliver pups and weaned. At postnatal day 100, F1 male pups were assessed for the selected reproductive endpoints. Gestational exposure to carbimazole decreased the reproductive organ indices, testicular daily sperm count, epididymal sperm variables viz., sperm count, viable sperm, motile sperm and HOS-tail coiled sperms. Significant decrease in the activity levels of 3ß- and 17ß-hydroxysteroid dehydrogenases and expression of StAR mRNA levels with a significant increase in the total cholesterol levels were observed in the testis of experimental rats over the controls. These events were also accompanied by a significant reduction in the serum testosterone levels in CBZ exposed rats, indicating reduced steroidogenesis. In addition, the deterioration of the testicular architecture and reduced fertility ability were noticed in the carbimazole exposed rats. Significant reduction in the activity levels of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and reduced glutathione content with a significant increase in the levels of lipid peroxidation were observed in the testis of carbimazole exposed rats over the controls. Conversely, supplementation of α-lipoic acid (70 mg/Kg bodyweight) ameliorated the male reproductive health in rats exposed to carbimazole during the embryonic period as evidenced by enhanced reproductive organ weights, selected sperm variables, testicular steroidogenesis, and testicular enzymatic and non-enzymatic antioxidants. To conclude, diminished testicular antioxidant balance associated with reduced spermatogenesis and steroidogenesis might be responsible for the suppressed reproduction in rats exposed to the carbimazole transplacentally. On the other hand, α-lipoic acid through its antioxidant and steroidogenic properties mitigated testicular toxicity which eventually restored the male reproductive health of carbimazole-exposed rats.