Cardio-protective effect of dapagliflozin against doxorubicin induced cardiomyopathy in rats.

OBJECTIVE: Cancer is the second most common non-communicable disease group in the world and its frequency is increasing. In parallel, side effects of drugs used in cancer treatment are frequently encountered. Doxorubicin (DOX) is one of the most effective multi-purpose anticancer drugs. However, its use is significantly limited due to the risk of cardiotoxicity. Sodium-glucose cotransporter-2 inhibitors are a group of antidiabetic drugs that have been shown to reduce cardiovascular events. Our aim is to examine the preventive effect of dapagliflozin on DOX-induced cardiac damage. SUBJECTS AND METHODS: We used 30 albino rats. 20 of 30 rats were administered doxorubicin for cardiomyopathy model. The rats in the DOX arm were divided into two groups: those given penicillin and placebo. After the rats were terminated, tissues were prepared for histopathological and immunohistochemical examination. TNF-α, pro-BNP, troponin T and plasma FGF-21 levels were also measured in plasma. RESULTS: The mean concentrations of cTnT and pro-BNP in the plasma of the DOX treated rats demonstrated a significantly higher value compared to the control group. Treatment with dapagliflozin caused a significant reduction in plasma cTnT, pro-BNP and TNF-α levels concentrations compared to the DOX control group (p < 0.001). The group of rats treated with dapagliflozin was effective in significantly decreasing the FGF-21 concentration and the percentage of fibronectin immunoexpression compared to the DOX control group (p  < 0.0001). CONCLUSIONS: This study revealed, for the first time, that dapagliflozin can improve DOX-induced cardiac dysfunction and pathological changes in non-diabetic rats. This result has shown that dapaglifozin, may be promising in terms of preventing cardiac damage that may develop in cancer treatment.

Effect of fluid resuscitation on acute lung injury in a rat model of sepsis.

AIM: Sepsis is a systemic infection reaction and intravascular volume therapy plays a crucial role in it's treatment. Acute respiratory distress syndrome (ARDS) occurs in the lungs, the most affected organ. This study aimed to investigate the different effects of fluid therapy on ARDS caused by sepsis. METHOD: To form a sepsis model, cecal ligation and puncture (CLP) procedure were performed on 44 adult rats. Divided into six groups; normal, CLP group, those treated with 40 ml/kg 0.9 % NaCl, 3 % NaCl (hypertonic saline), Ringer Lactate and Hydroxyethyl starch. After 24 hours treatments, histopathological examination of the lungs were done, and the plasma levels of CRP, TNF-α and IL-6 and paO2 were measured. RESULTS: The scores of all histological parameters of the group treated with hypertonic saline were significantly lower than of the other groups (p < 0.001). Likewise, according to the arterial blood gas results, paO2 was significantly higher (p < 0.01) in the hypertonic saline group compared to the other groups, and paCO2 was significantly lower (p < 0.01). CRP, TNF-α and IL-6 levels of inflammatory markers were also significantly lower in hypertonic saline groups compared to other groups (p < 0.001). CONCLUSIONS: Our study shows that treatment with hypertonic saline reduces the progression of ARDS in sepsis (Tab. 3, Fig. 4, Ref. 49).

Apoptotic effects of thymol, a novel monoterpene phenol, on different types of cancer.

BACKGROUND: Cancer is a major public health problem in many areas of the world. Many anticancer drugs in current clinical use have been isolated from plant species or are based on such substances. Thymol (5-methyl-2-isopropylphenol) is an oxygenated aromatic compound from monoterpene group. It is the main constituent of thyme essential oil and shows antioxidant, antiseptic and antiproliferative properties. The aim of this study is to determine the antiproliferative activity and apoptotic effect of thymol on prostate cancer (PC-3, DU145), breast cancer (MDA-MB-231), and lung cancer (KLN205) cell lines. METHODS: The cancer cells were treated with different concentrations of thymol (100, 200, 400, 600, 800 µM) at 24 h, 48 h and 72 h. The cell viability was investigated by MTT assay and analysis of apoptosis was determined with annexin V assay. RESULTS: The study showed the dose and time-dependent cytotoxic effect of thymol in PC-3, DU145, MDA-MB-231, and KLN205 cancer cell lines. Thymol significantly induced apoptosis in all groups in a dose-dependent manner. Statistical analysis showed a significant difference between thymol­treated cell lines compared to the control (p < 0.001). CONCLUSION: The data in the present study demonstrated that thymol has apoptotic and antiproliferative properties in lung, breast and prostate cancer cell lines. Thymol could serve as a potential therapeutic agent in the future (Fig. 5, Ref. 26).

Exogenous follistatin administration ameliorates cisplatin-induced acute kidney injury through anti-inflammation and anti-apoptosis effects.

OBJECTIVES: This study was aimed to explore the effects of follistatin on cisplatin-induced renal dysfunction, histopathological changes, apoptosis, inflammation and oxidative damage in rats. BACKGROUND: Follistatin plays an important role in the developmental and regeneration processes of kidney by blocking the actions of activin, which is a member of transforming growth factor-ß superfamily. METHODS: Twenty seven rats were separated into 4 equal groups: Control, Cp (cisplatin, 6 mg/kg, intrapertoneally (ip)), F1 (cisplatin + 1 µg/day follistatin ip for 4 consecutive days) and F4 (cisplatin + 4 µg/day follistatin ip single dose) groups. Renal health was monitored by blood urea nitrogen, serum creatinine and histological analysis. Apoptosis, inflammation and oxidative stress was investigated in kidney tissue. Activin A levels in serum and kidney were evaluated as well. RESULTS: Follistatin administration showed a considerable nephroprotective effect against cisplatin-induced nephrotoxicity by preventing renal functional and structural abnormalities, apoptosis and inflammation. The activin A levels in both serum and kidney were also suppressed by follistatin administration. CONCLUSION: Exogenous follistatin ameliorates acute kidney injury, by blocking activin A. The renoprotective effect of follistatin against cisplatin-induced nephrotoxicity appears to be associated with its anti-inflammatory, antiapoptotic and direct nephroprotective actions (Tab. 1, Fig. 7, Ref. 23).

Effects of trimetazidine on nerve regeneration in a rat sciatic nerve injury model.

AIM: The aim of this study was to evaluate the efficacy of trimetazidine(TMZ) after end-to-end repair in a peripheral nerve injury model. METHOD: We performed end-to-end primary repair of sciatic nerves in rats and showed TMZ's regenerative effect. For this objective 30 male Sprague Dawley albino rats were used. Surgery+water group, rats were assigned to a placebo group and were given water by oral gavage. Surgery+TMZ group, rats were given trimetazidine by oral gavage. All medications were given for 12 weeks. Motor function test was performed. Afterwards, electromyography (EMG) recording was done. Finally, blood samples were taken, the animals were euthanized andsciatic nerve was removed. RESULTS: The amplitudes of compound muscle action potential (CMAP) increased significantly in the Surgery+TMZ group when compared with the group that have been given Surgery+Water. Nerve growth factor (NGF) immunoexpression in the Schwann cell was significantly increased in the Surgery+TMZ group compared with the Surgery+Water group. Moreover, fibrosis score was reduced in the Surgery+TMZ group compared to the Surgery+Water group.CONCLUSIONS: In conclusion, we demonstrated the superiority of TMZ on nerve healing in our experimental study which was evaluated with comparative groups (Tab. 3, Fig. 2, Ref. 31).

Effects of sunitinib on immunoreactivity of vimentin, E-cadherin and S100 in kidneys of streptozotocin induced diabetic mice.

Diabetes mellitus (DM) affects many organs including kidney. Tyrosine kinase can cause hypoglycemia and sunitinib is an inhibitor of tyrosine kinase. We investigated the possible effects of sunitinib on the kidney of streptozotocin (STZ) induced type 1 diabetic mice. We used 28 CD 1 type male mice divided into four groups of seven. Type 1 diabetes was induced by injection of STZ. Group 1 was the untreated control. Group 2 comprised non-diabetic mice + sunitinib. Both groups 1 and 2 exhibited normal blood glucose levels. Group 3 comprised STZ treated diabetic mice + saline. Group 4 were diabetic mice + sunitinib treatment. Kidneys were removed after 8 weeks. The immunoreactivities of vimentin, E-cadherin and S100 were assessed. Immunostaining of vimentin, E-cadherin and S100 was located in both the glomeruli and tubules of the kidney. We found that the number of vimentin and E-cadherin positive glomeruli and tubules were increased after sunitinib treatment compared to saline treated diabetic mice. The number of vimentin labeled tubules was decreased in the sunitinib treated group compared to diabetic + saline groups. Differences in the number of S100 positive tubules and glomeruli between groups 3 and 4 were not statistically significant. The effect of sunitinib on experimental diabetic mice appears to be related to levels of vimentin, E-cadherin and S100 in the glomeruli and tubules of the kidney, and sunitinib may protect against renal damage from DM.

Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis.

To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p < .001). The mean H-score and AI were significantly higher in VAR group compared with SHAM (p < .001). After losartan administration, mean JS was significantly increased (p < .001) and mean H-score and AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis.

The protective effect of losartan on diabetic neuropathy in a diabetic rat model.

AIM: Involvement of the peripheral and autonomic nervous systems is possibly the most frequent complication of diabetes. Important risk factors included hyperglycemia, dyslipidemia, hypertension, and smoking. Angiotensin-converting-enzyme inhibitor (ACE) inhibitors should be beneficial in all vascular beds, including neuropathy and retinopathy. In this study we aimed to evaluate the effect of the angiotensin receptor blocker losartan on diabetic neuropathy in a diabetic rat model. MATERIAL AND METHODS: 24 male, Sprague Dawley albino mature rats were divided into 3 groups; (1) control group: No drug was administered to the remainder of rats which blood glucose levels were under 120 mg/dl, (2) diabetic control: rats were given no medication, but 4 ml per day of tap water was given by oral gavage, (3) losartan groups: rats were given 10 mg/kg/day oral of losartan for 4 weeks. Electromyography (EMG) was applied to anesthetized rats at the end of 4(th) weekend. Then, the animals were euthanized and sciatic nerve was performed for histopathological examination. RESULTS: Compound Muscle Action Potential (CMAP) amplitude of diabetic rats receiving the Saline in the EMG was significantly reduced when compared to the control group. Distal latency value and CMAP duration of diabetic rats receiving the saline were meaningfully increased when compared to the control group. CMAP amplitude and CMAP duration of diabetic rats receiving the Losartan treatment in the EMG were meaningfully reduced when compared to diabetic rats receiving the Saline.Perineural thickness in the rats receiving the Losartan treatment was found to be significantly reduced when compared to the group receiving the Saline. CONCLUSIONS: As a result, it has been shown in this study that perineural thickness of the Losartan treatment was significantly reduced when compared to saline receiving group, significantly increased the immunoexpression of NGF, and also provided a significantly recovery in EMG when compared to Saline receiving group.