Cadmium as an ovarian toxicant: A review.

Cadmium (Cd) is a ubiquitous heavy metal toxicant with no biological function in the human body. Considerably, because of its long biological half-life and very low excretion rate, Cd is inclined to accumulate and cause deleterious effects on various body organs (e.g., liver, kidney, and ovary) in humans and animals. Ovaries are the most vulnerable targets of Cd toxicity. Cd has been shown to induce oxidative stress, follicular atresia, hormonal imbalance, and impairment of oocyte growth and development. Moreover, Cd toxicity has been associated with increasing incidences of menstrual disorders, pregnancy loss, preterm births, delayed puberty, and female infertility. Therefore, it is crucial to understand how Cd poisoning impacts specific ovarian processes for the development of preventive interventions to enhance female fertility. The current review attempts to collate the recent findings on Cd-induced oxidative stress, follicular apoptosis, steroid synthesis inhibition, and teratogenic toxicity, along with their possible mechanisms in the ovarian tissue of different animal species. Additionally, the review also summarizes the studies related to the use of many antioxidants, medicinal herbs, and other compounds as remedial approaches for managing Cd-induced ovarian toxicity.

Chemotherapeutic drugs induced female reproductive toxicity and treatment strategies.

Increase in success of cancer treatment with advancement in the screening, prognosis and diagnosis protocols have significantly improved the rate of cancer survivorship. With the declining cancer mortality, however, the cancer survivors are also subjected to the adverse consequences of chemotherapy, particularly in the female reproductive system. Recent studies have shown the sensitivity of the ovarian tissue to the chemotherapeutic drugs-induced toxicity. Several in vitro and in vivo studies have assessed the toxic effects of chemotherapeutic drugs. The most frequently used chemotherapeutic drugs such as doxorubicin, cyclophosphamide, cisplatin and paclitaxel have been reported to cause ovarian damage, diminution of follicular pool reserve, premature ovarian failure and early menopause, resulting into declining fertility potential among females. The chemotherapy often employs combination of drug regimen to increase the efficacy of the treatment. However, the literature mostly consists of clinical data regarding the gonadotoxicity caused by anticancer drugs but there lacks the understanding of toxicity mechanism. Therefore, understanding of the different toxicity mechanisms will be helpful in development of possible therapeutic interventions for preservation of declining female fertility among cancer survivors. The current review comprehends the underlying mechanisms of female reproductive toxicity induced by the most commonly used chemotherapeutic drugs. In addition, the review also summarizes the recent findings related to the use of various protectants to diminish or at least in managing the toxicity induced by different chemotherapeutic drugs in females.

Tail approach synthesis of triazolylthiazolotriazole bearing benzenesulfonamides as carbonic anhydrase inhibitors capable of inducing apoptosis.

Inhibition of human carbonic anhydrase (hCA) isoform IX with concurrent induction of apoptosis is a promising approach for targeting cancer in humans. Prompted by the scope, novel benzenesulfonamides containing the 1,2,3-triazolylthiazolotriazole tail were synthesized and screened as inhibitors of hCA isoforms I, II, IV, and IX. The tumor-associated isoform hCA IX was strongly inhibited by the sulfonamides reported here with KI values ranging from 45 nM to 1.882 µM. Overall, nine compounds showed hCA IX inhibition with KI < 250 nM. The glaucoma-associated isoform hCA II was moderately inhibited while the cytosolic isoform hCA I and membrane-bound isoform hCA IV were weakly inhibited by the synthesized sulfonamides. Compound 6Ac (KI = 3.6 nM) was found to be an almost three times more potent inhibitor of hCA II as compared to the standard drug acetazolamide (KI = 12.1 nM). The selective hCA IX inhibitors were further studied for their apoptotic efficacy in goat ovarian cells and showed better results as compared to the control. A comparative study of previously synthesized compounds and molecular docking study of representative compounds revealed some important generalizations that could prove beneficial in further investigations of isoform-selective hCA inhibitors.