Melatonin abrogates liver, ovarian, and uterine toxicities induced by tamoxifen in a breast cancer mouse model

33-43Melatonin is known for its efficacy in breast cancer treatment. However, the safety profile of melatonin, particularly its effect on liver, uterus and ovaries is largely unknown. Here, we explored the safety profile of melatonin using virgin female mice of the Swiss albino strain. Further, we investigated whether melatonin can overcome liver, ovaries and uterine toxicities which are induced by tamoxifen using N,N-dimethylbenzylamine (DMBA) induced breast cancer mouse model? Treatment of tamoxifen after breast cancer induction in mice resulted in reduction of breast masses but severe pathological abnormalities like liver steatosis, hyper ovulation, ovarian cysts, uterine glands dilatations and endometriosis were observed in treated animals. Whereas, melatonin when used in combination with tamoxifen helped to reduce the mouse mammary tumor volume and significantly decreases liver enzymes, steroid hormones and oxidative stress. Melatonin also reverted the liver, ovarian and uterus toxicity induced by tamoxifen. The results have demonstrated that tamoxifen when used as combination therapy with melatonin serve as an effective anti-breast cancer molecule with minimum liver, ovarian and uterus toxicities

Melatonin abrogates liver, ovarian, and uterine toxicities induced by tamoxifen in a breast cancer mouse model

Melatonin is known for its efficacy in breast cancer treatment. However, the safety profile of melatonin, particularly its effect on liver, uterus and ovaries is largely unknown. Here, we explored the safety profile of melatonin using virgin female mice of the Swiss albino strain. Further, we investigated whether melatonin can overcome liver, ovaries and uterine toxicities which are induced by tamoxifen using N,N-dimethylbenzylamine (DMBA) induced breast cancer mouse model? Treatment of tamoxifen after breast cancer induction in mice resulted in reduction of breast masses but severe pathological abnormalities like liver steatosis, hyper ovulation, ovarian cysts, uterine glands dilatations and endometriosis were observed in treated animals. Whereas, melatonin when used in combination with tamoxifen helped to reduce the mouse mammary tumor volume and significantly decreases liver enzymes, steroid hormones and oxidative stress. Melatonin also reverted the liver, ovarian and uterus toxicity induced by tamoxifen. The results have demonstrated that tamoxifen when used as combination therapy with melatonin serve as an effective anti-breast cancer molecule with minimum liver, ovarian and uterus toxicities

Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice

Background: Kidney is a vital organ which plays an important and irreplaceable role in detoxification and removal of xenobiotics. And therefore is vulnerable to develop various forms of injuries. Hence, making it immensely important to search for natural reno-protective compounds. Objectives: This study therefore, aims to evaluate the reno-protective properties of propolis against gentamicin induced renal toxicity in mice. Methods: Three groups of 10 male mice each were used for this study. First group served as control, the second group (Gm group) was administered orally 80 mg/kg body weight gentamicin for 7 days, and the third group (GmP group) was administered same dose of gentamicin with propolis (500 mg/kg body weight) for 7 days. Various parameters were used to study the renal toxicity. Results: Gentamicin caused significant renal damage as evident by the rise in BUN levels, diminished glomeruli hypocellularity, moderately dilated tubules, and mild loss of brush border, severe infiltration, extensive tubular degeneration and presence of tubular cast. Histochemistry results show presence of collagen and reticular fibres. Immunohistochemical reactions show kidney injury (Kim-1 gene-expression), oxidative stress (MDA gene-expression), and an increase in apoptosis (caspase-3 gene-expression). Co-administration of propolis with gentamicin showed significant decrease in BUN levels, appearance of healthy glomeruli with normal cellularity, reduction of tubular injury, decrease of collagen and reticular fibres deposition, reduction of apoptosis, kidney injury and oxidative stress. Conclusion: Results presented in this study clearly show the reno-protective role of propolis against gentamicin-induced toxicity on mice kidney

Hypertensive disorders in women with peripartum cardiomyopathy: insights from the ESC EORP PPCM Registry

Aims: Hypertensive disorders occur in women with peripartum cardiomyopathy (PPCM). How often hypertensive disorders co-exist, and to what extent they impact outcomes, is less clear. We describe differences in phenotype and outcomes in women with PPCM with and without hypertensive disorders during pregnancy. Methods: The European Society of Cardiology PPCM Registry enrolled women with PPCM from 2012-2018. Three groups were examined: 1) women without hypertension (‘PPCM-noHTN’); 2) women with hypertension but without pre-eclampsia (‘PPCM-HTN’); 3) women with pre-eclampsia (‘PPCM-PE’). Maternal (6-month) and neonatal outcomes were compared. Results: Of 735 women included, 452 (61.5%) had PPCM-noHTN, 99 (13.5%) had PPCM-HTN and 184 (25.0%) had PPCM-PE. Compared to women with PPCM-noHTN, women with PPCM-PE had more severe symptoms (NYHA IV in 44.4% and 29.9%, p<0.001), more frequent signs of heart failure (pulmonary rales in 70.7% and 55.4%, p=0.002), higher baseline LVEF (32.7% and 30.7%, p=0.005) and smaller left ventricular end diastolic diameter (57.4mm [±6.7] and 59.8mm [±8.1], p<0.001). There were no differences in the frequencies of death from any cause, re-hospitalization for any cause, stroke, or thromboembolic events. Compared to women with PPCM-noHTN, women with PPCM-PE had a greater likelihood of left ventricular recovery (LVEF≥50%) (adjusted OR 2.08 95% CI 1.21-3.57) and an adverse neonatal outcome (composite of termination, miscarriage, low birth weight or neonatal death) (adjusted OR 2.84 95% CI 1.66-4.87). Conclusion: Differences exist in phenotype, recovery of cardiac function and neonatal outcomes according to hypertensive status in women with PPCM