Protective effects of necrostatin-1 on doxorubicin-induced cardiotoxicity in rat heart.

Background: Doxorubicin (Dox) is one of the most effective antineoplastic drugs which has severe cardiotoxic effects, limiting its clinical usage. Though the exact mechanism of doxorubicin-induced cardiotoxicity is yet to be elucidated, it is shown that production of reactive oxygen species (ROS) increases oxidative stress and leads to cardiomyocyte apoptosis and necroptosis which is also defined as a programmed cell death.Purpose: In the present study, we investigate the effects of necrostatin-1 (Nec-1)-an inhibitor of receptor interaction proteins 1 (RIP1) and necroptosis-on doxorubicin-induced cardiotoxicity in rats.Research Design: Hearts were isolated and perfused by the Langendorff system in all four groups. Perfusion pressure (PP), left ventricular developed pressure (LVDP) and heart rate per minute (HR), LV (dP/dt) max, and LV (dP/dt) min which shows cardiac contractility and relaxation were recorded.Results: Results showed that PP significantly increased with Dox treatment and significantly decreased with Nec-1 treatment, while HR, LVDP, LV (dP/dt) max, and LV (dP/dt) min values significantly decreased with the Dox-treated group and significantly increased with Nec-1 treatment. Also with Nec-1 treatment, gene expression levels of anti-apoptotic Bcl-2 significantly increased and pro-apoptotic protein Bax, apoptotic marker caspase-3, and Nox-2 significantly decreased compared to the Dox-treated group. In heart tissues, MDA levels were significantly increased with Dox and decreased with Nec-1 treatment. These results were supported by the histological analysis indicated that Nec-1 reduced doxorubicin-induced cellular injury.Conclusions: In conclusion, our data indicate that Nec-1 ameliorates doxorubicin-induced cardiotoxicity by reducing oxidative stress injury and attenuating apoptosis and necroptosis.

A case-control study on depression, anxiety, and belief in sexual myths in trans women.

Objective: The purpose of our study was to investigate depression, anxiety, and belief in sexual myths in trans women. Methods: This is a prospective case-control study. The case group included 60 trans women who were referred to the Medical Biology and Genetics Department from various clinics of the research and training hospital where this study was conducted. The control group consisted of 60 healthy male individuals who presented to the same hospital for routine health follow-ups and collecting documents showing their health. In data collection, we used a Personal Information Form, the Sexual Myths Scale, and the Beck Depression and Anxiety Inventories. The IBM Statistical Package for the Social Sciences 25.0 was used to analyze the data. Results: In the case group, 26.7% of the participants were sex workers, and all were single. While 46.7% of the participants in the case group were living with their families, 66.7% were smokers, and 13.3% were receiving hormone treatment. All 60 participants in the control group were also single. The participants in the control group had higher levels of believing sexual myths and lower levels of anxiety and depression than those in the case group (p = 0.000). The mean scores of the participants in the control group in the Sexual Orientation and Sexual Violence subscales of the Sexual Myths Scale were higher than the mean scores of those in the case group (p < 0.05). Conclusion: The trans women who participated in this study had higher levels of anxiety and depression and lower levels of believing sexual myths than the control group. The mental health of trans women can be disrupted due to various treatments they are exposed to in society such as stigma, discrimination, and violence. Their higher anxiety and depression levels in this study could be explained by this exposure. This exposure could also have led to their lower total scores in the Sexual Myths Scale, as well as lower scores in the Sexual Violence and Sexual Orientation subscales.

Metformin HCl has curative effect on rebuilding of ventricular diastolic functions in high-fat-diet fed rats.

Myocardial lipid accumulation due to diabetes and/or obesity plays a role in the progression of left ventricular diastolic dysfunction. Our aims were to exhibit the correlation between histopathologic stage of the liver and cardiac functions, and to evaluate the effects of metformin HCl and rosiglitazone on myocardial functions. Thirty-two male Sprague-Dawley rats were divided into four groups to exhibit the correlation between histopathologic stage of the liver and cardiac functions and to determine whether metformin HCl and rosiglitazone have effects on cardiac functions. For 20 weeks, one group was fed standard rat basic diet, whereas the other groups were on high-fat-diet. During the last 4 weeks, metformin HCl was given to the third group, rosiglitazone to the fourth group. Histological evaluation of rat livers yielded significantly higher steatosis grade in high-fat-diet group and different fibrosis stages among groups. Also, there was significant correlation between diastolic functions and steatosis grade/fibrosis stage of rat liver. Electrophysiological study of hearts via Langendorff technique showed better coronary perfusion pressures and diastolic functions in standard-diet and metformin HCl groups compared to other groups. Metformin HCl improves LV diastolic dysfunction and coronary perfusion pressures.

Impact of N-acetylcysteine and etodolac treatment on systolic and diastolic function in a rat model of myocardial steatosis induced by high-fat-diet.

OBJECTIVES: Obesity is a worldwide problem, leading to cardiomyopathy. Oxidative stress and inflammation have been reported to play significant roles in developing obesity cardiomyopathy. N-acetylcysteine is a glutathione prodrug that preserves liver against steatosis via constraining the production of reactive oxygen species. Etodolac is a nonsteroidal anti-inflammatory drug which has been demonstrated to protect liver against fibrosis. The aim of the present study was to evaluate and compare the effects of N-acetylcysteine and etodolac on impaired cardiac functions due to high-fat-diet (HFD) induced myocardial steatosis in rats. MATERIAL AND METHODS: Thirty-two male Sprague-Dawley rats were randomly divided into four groups. Control group was maintained on standard-rat-basic-diet (SD) for 20 weeks, while HFD was given to three study groups for 20 weeks. Then N-acetylcysteine was given to one of the study groups (HFD+NAC), and etodolac to another group (HFD+ETD) as a supplement for 4 weeks while all groups were continued on SD. At the end of the study periods, hearts were examined by Langendorff technique and rat livers were evaluated histologically. RESULTS: HFD and HFD+ETD groups presented with significantly higher steatosis and fibrosis in liver compared to other groups. HFD+NAC preserved diastolic functions. Also HFD+NAC and HFD+ETD groups had significantly better systolic funtions than HFD group. CONCLUSIONS: Obesity is associated with diastolic dysfunction rather than systolic dysfunction. NAC may protect the heart against diastolic dysfunction due to obesity. NAC and etodolac treatment improve systolic function, even in the absence of systolic dysfunction.

Protective effects of ethyl pyruvate in cisplatin-induced nephrotoxicity.

This study was performed to investigate the effect of ethyl pyruvate on changes in renal functions and oxidative stress related renal injury caused by cisplatin (cis-dichlorodiammine platinum-II; CDDP). Male Wistar albino rats were divided into four groups (n = 8): (1) control group (1 ml Ringer's lactate solution i.p.); (2) ethyl pyruvate (EP) group (50 mg/kg Ringer's EP solution (REPS) i.p.); (3) cisplatin group (a single dose of cisplatin (5 mg/kg, i.p.); and (4) cisplatin + EP group (a single dose of cisplatin (5 mg/kg, i.p.) + REPS 50 mg/kg/day, i.p.) for five days. At the sixth day, kidneys of rats were mounted to a Langendorff apparatus. Renal perfusion pressures were recorded. Blood samples were taken for serum urea, creatinine, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stres index (OSI) evaluations. Kidney tissues were obtained for malondialdehyde (MDA) analyses and histopathological examination. Perfusion pressures, serum urea, creatinine, TOS, OSI and tissue MDA levels were found significantly higher, whereas TAS was notably lower in cisplatin group. Histopathological examination showed apparent renal paranchymal injury in cisplatin group. In cisplatin + REPS group, perfusion pressures, serum urea, creatinine and tissue MDA levels were decreased. Moreover, EP co-administration provided less inflammatory cell infiltration, tubular dilatation, whereas TOS, TAS and OSI improved significantly versus cisplatin group. These findings show that EP has protective effects against cisplatin nephrotoxicity.

Oxytocin ameliorates remote liver injury induced by renal ischemia-reperfusion in rats.

Renal ischemia-reperfusion (IR) causes remote liver damage. Oxytocin has anti-inflammatory and antioxidant effects. The main purpose of this study was to evaluate the protective function of oxytocin (OT) in remote liver damage triggered by renal IR in rats. Twenty four rats were randomly divided into four different groups, each containing 8 rats. The groups were as follows: (1) Sham operated group; (2) Sham operated+OT group (3) Renal IR group; (4) Renal IR+OT group. OT (500µg/kg) was administered subcutaneously 12 and 24 hours before and immediately after ischemia. At the end of experimental procedure, the rats were sacrificed, and liver specimens were taken for histological assessment or determination of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1) activity and nitric oxide (NO). The results showed that renal IR injury constituted a notable elevation in MDA, TOS, Oxidative stress index (OSI) and significantly decreased TAS, PON-1 actvity and NO in liver tissue (p<0.05). Additionally renal IR provoked significant augmentation in hepatic microscopic damage scores. However, alterations in these biochemical and histopathological indices due to IR injury were attenuated by OT treatment (p<0.05). These findings show that OT ameliorates remote liver damage triggered by renal ischemia-reperfusion and this preservation involves suppression of inflammation and regulation of oxidant-antioxidant status.