Design, synthesis, biological evaluation, and computational studies of novel thiazolo-pyrazole hybrids as promising selective COX-2 inhibitors: Implementation of apoptotic genes expression for ulcerogenic liability assessment.

Exposure to toxic metals including cadmium has become an increasingly recognized source of illness worldwide. Cadmium (Cd2+) is one of the environmental pollutants affecting various tissues and organs including testis. The protective effect of lipoic acid and selenium on Cd2+‐induced testicular damage was investigated. Accordingly, male Wistar rats were allocated into four groups (n = 8; each). Gp I: (control), whereas the other 3 groups received CdCl2 (2 mg/kg, i.p. for 28 days) alone or in combination with either (i) lipoic acid (35 mg/kg, p.o) or (ii) selenium (0.35 mg/kg, p.o) throughout the experiment. Serum testosterone, luteinizing hormone and follicle‐stimulating hormone levels significantly decreased in the Cd2+‐exposed rats. The activities of testicular key androgenic enzymes, 3β‐hydroxysteroid dehydrogenase and 17 β‐HSD significantly decreased in Cd2 exposed rats compared to the control counterparts. In addition, the activities of testicular marker enzymes were significantly altered in cadmium‐treated animals. Significant reductions in body and testicular weight as well as antioxidant status were also observed in Cd2+‐exposed rats. Moreover, some testicular metal levels were altered. Lipoic acid and selenium significantly increased serum testosterone level and restored testicular activity of 3β‐HSD and 17 β‐HSD and were effective in modulation of most of the measured biochemical parameters. The biochemical parameters were further confirmed with histopathological findings. In conclusion, the present study demonstrated the beneficial influences of lipoic acid and selenium in reducing harmful effects of Cd2+ in rats' testes. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:15–25 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20354

Modulatory effects of lipoic acid and selenium against cadmium-induced biochemical alteration in testicular steroidogenesis

Novel 5,6-diphenyl-1,2,4-triazine-3-thiol derivatives as dual COX-2/5-LOX inhibitors devoid of cardiotoxicity.

The aim of the present study was to investigate the ameliorative potential of parsley (Petroselinum crispum) leaf essential oil (PO) against the detrimental effects of carbon tetrachloride (CCl4) on the thyroid gland and testes of mice. Twenty-four adult male mice were divided into four groups and treated for 4 weeks. The 1st control group received 3 mL/kg olive oil intraperitoneally, twice a week followed by 0.5 mL/kg saline intragastrically daily. The 2nd CCl4 group received CCl4 (3 mL/kg intraperitoneally, twice a week). The 3rd PO group received PO (0.5 mL/kg intragastrically daily), while the 4th CCl4+PO group received CCl4 coadministrated with PO at the aforementioned doses. CCl4 group recorded significant ( ) reduction in the activities of antioxidant enzyme catalase (CAT) and superoxide dismutase (SOD) and significant ( ) increase in the lipid peroxidation end product’s level malondialdehyde (MDA) in the testes and thyroid glands. Meanwhile, serum levels of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid hormones (thyroid-stimulating hormone (TSH), total triiodothyronine (T3), free triiodothyronine (fT3), total thyroxine (T4), and free thyroxine (fT4)) significantly decreased. Also, histopathologically, the testicular tissue showed hypospermatogenesis within irregular-shaped seminiferous tubules with prominent edema in the interstitial spaces confirming the aforementioned biochemical alterations. Treatment with PO significantly reduced the testicular and thyroid oxidative stress ( ) and elevated the testosterone (73.47%), FSH (92.11%), LH (33.33%), T3 (23.47%), fT3 (39.13%), T4 (27.91%), and fT4 (75%) as compared to that of CCl4-treated group corresponding values. The PO GC/MS analysis indicated bioactive monoterpenes (major component is 1,3,8-mentha triene 34.48%) and phenylpropenes (major component is myristicin 21.04%). Results suggested the ameliorative effect of PO against CCl4-induced hypogonadism in mice by suppressing oxidative stress and maintaining thyroid gland function.

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Antioxidant Potential of Parsley Leaf (Petroselinum crispum) Essential Oil on Hypothyroidism and Testicular Injury in Mice Intoxicated by Carbon Tetrachloride.

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Effect of Induced hypothyroidism by Propiltiouracil (PTU) on Serum Levels of Testosterone, Luteinizing Hormone, Follicle Stimulating Hormone in Adult Rat

Background: The objective of this study is to evaluate the influence of carbimazole- induced hypothyroidism on the testes of adult albino rats and the probable protective effect of alpha-lipoic acid (ALA). Materials and methods: The rats were divided into four groups; control group, ALA group, carbimazole, and carbimazole + ALA groups. Rats were exposed to ALA (60 mg/kg body weight) or carbimazole (1.35 mg/kg body weight), or both, administered via gavages for 30 days. Results: Morphometric analysis revealed a significant decrease in tubular diameter, germinal epithelium thickness, and interstitial space as compared to the controls. Also, rats exposed to carbimazole showed a significant decline in testicular weight, sperm motility, and count. Additionally, deterioration of the testicular architecture was observed. ALA supplementation resulted in a significant improvement in the tubular diameter and germinal epithelium thickness, but no significant improvement regarding interstitial space was observed. Another observation was the significant decline in serum testosterone and follicle-stimulating hormone (FSH) in the carbimazole group, indicating reduced steroidogenesis. A significant reduction in reduced glutathione content was detected in the testes of the carbimazole group compared with the controls, while malonaldehyde concentration significantly increased. Conversely, ALA supplementation ameliorated the toxicity induced by hypothyroidism as illustrated by enhanced reproductive organ weights, testosterone, luteinizing hormone, and FSH levels, testicular steroidogenesis, and oxidative stress parameters. Conclusions: Hypothyroidism altered testicular antioxidant balance and negatively affected spermatogenesis. On the other hand, ALA through its antioxidant properties alleviated testicular toxicity in carbimazole-exposed rats.

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Hypothyroidism: morphological and metabolic changes in the testis of adult albino rat and the amelioration by alpha-lipoic acid