Effect of thymoquinone on transient receptor potential melastatin (TRPM) channels in rats with liver ischemia reperfusion model in rats.

Objectives: We aimed to investigate the levels of transient receptor potential melastatin (TRPM) gene expression, and the antioxidant and histopathologic effect of thymoquinone (Tmq) in the hepatic I/R rat model. Materials and Methods: Fifty Wistar rats were divided into 5 groups. Group 1: Control; Group 2: Sham; Group 3: Hepatic I/R (45 min/45 min); Group 4: Tmq (50 mg/kg); Group 5: Tmq+I/R (ten days before I/R at the dose of 50 mg/kg of Tmq). The hepatic I/R (45min/45min) model was performed at the portal vein and the hepatic artery with atraumatic vascular clamp in the ischemia groups. The liver tissues and blood samples that were taken at the end of the study were evaluated for histopathologic and biochemical analysis. Besides TRPM gene expression levels were determined in liver tissues. It was seen that cellular swelling, congestion, PNL, and apoptosis parameters statistically decreased in Tmq and Tmq+I/R groups in comparison with the I/R group in histopathological evaluation. Results: It was observed that biochemical parameters, AST, ALT, GGT, LDH, creatinine, and urea levels significantly increased in the I/R group as compared with, sham, Tmq, and Tmq+I/R groups. It was found that TRPM2,6,7,8 gene expression decreased significantly in Tmq+I/R groups as compared to the I/R group. Conclusion: We showed that thymoquinone can inhibit the entry of Ca+2 into the cell by decreasing TRPM2,6,7,8 gene expression. Based on our findings, we think that Tmq application in the treatment of liver diseases due to I/R damage may be important in terms of both ischemia and apoptosis and can also be used in the treatment of liver-related diseases.

Behavioral and Cognitive Consequences of Obesity in Parents and Offspring in Female and Male Rats: Implications of Neuroinflammation and Neuromodulation.

Obesity is a rapidly growing public health concern that can create a family-wise burden. This study was aimed to investigate behavioral, cognitive, neuroinflammatory, and neuromodulatory consequences of the diet and parental obesity. Female and male Wistar albino rats were fed on either an obesogenic or standard diet for 12 weeks, beginning with weaning. Thereafter, the animals were matched and allowed to mate. Pups born to obese or normal parents received either the diet or standard chow to the same age. The obesogenic diet and/or parental obesity increased the locomotor activity in both females and males. The diet exhibited anxiolytic-like and antidepressant-like properties, and impaired short-term object memory as well as spatial memory. Interestingly, the obesogenic diet resulted in neuroinflammation only in naïve animals, but not in the ones with parental obesity. BDNF, SIRT1, and p53 expressions were decreased, whereas RelN expression was increased in the brain with the diet, regardless of parental obesity. Multi-factor analyses demonstrated that the obesogenic diet is the prominent influencer of cognitive, neuroinflammatory, and neuromodulatory results while parental obesity has an effect on spatial memory, neuroinflammation, and hippocampal RelN and p53 expressions. Here, we provided supporting evidence for detrimental cognitive and neuroinflammatory consequences of early life consumption of the obesogenic diet which accompanies alterations in neuromodulatory factors. Surprisingly, the diet was found beneficial against anxiety-like and depression-like behaviors, and additionally, parental obesity was demonstrated to impair some aspects of cognitive performance which appears unrelated to neuroinflammation.

CREB1 and PPAR-α/γ Pathways in Hepatic Ischemia/Reperfusion: Route for Curcumin to Hepatoprotection.

Background: Hepatic ischemia/reperfusion injury is a major problem that can exacerbate complications, particularly in liver transplantations. Objectives: This study aimed to investigate the cellular mechanisms of ischemia/reperfusion injury and hepatoprotection by curcumin. Methods: Wistar albino rats were divided into four groups as Control, Sham, I/R, and Cur+I/R. Hepatic ischemia/reperfusion was induced in I/R and Cur+I/R animals, the latter of which was also given 50 mg/kg/day of curcumin for 14 days. Liver aminotransferases and the transcription regulators of inflammation (RelA, IκB, PPAR-α, PPAR-γ, CREB1) were examined along with the histological examination. Results: Hepatic ischemia/reperfusion was found to disrupt hepatic microstructure and downregulate PPAR-α, PPAR-γ, and CREB1 transcripts. Curcumin supplementation in hepatic ischemia/reperfusion recovered the structural organization and promoted the hepatocyte regeneration while increasing expressions of PPARs and CREB1. RelA and IκB were found unaltered, possibly due to the crosstalk between targeted transcripts by ischemia/reperfusion and curcumin. Conclusions: In sum, PPAR-α/γ and CREB1 were involved in hepatic ischemia/reperfusion and, moreover, were detected to be stimulated by curcumin. PPAR and CREB pathways were found to provide a route to hepatoprotection for curcumin supplementation as evidenced by the microstructural improvement.

Protective Effects of Colchicine on Testicular Torsion/Detorsion-Induced Ischemia/Reperfusion Injury in Rats.

PURPOSE: To evaluate the short-term use of colchicine on preventing ischemia-reperfusion injury after surgery in an experimental animal model. MATERIALS AND METHODS: A total of 40 rats were divided into five groups (n = 8). Sham (Sh), ischemia-reperfusion (I/R), I/R and colchicine-treated for once per-operatively (I/Rc1), I/R and colchicine-treated for 5 days postoperatively (I/Rc5), and I/R and placebo given for 5 days (I/Rp) groups. Testicular torsion was created by rotating the testicle 720o in clockwise direction and held for 3 hours. In group I/Rc1 30 minutes before detorsion, p.o. 1 mg/kg mL infusion of colchicine was given only once. In group I/Rc5, colchicine continued p.o. once daily for five days. Tissue malonyldialdehite (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured for evaluating the oxidative stress. Apoptosis levels shown with Caspase-3 staining and mean seminiferous tubular diameter (MSTD), germinal epithelial cell thickness (GECT), and mean testicular biopsy score (MTBS) were used to evaluate the germ cell damage. RESULTS: Decreased protein MDA levels therewithal increased SOD, CAT and GPx levels achieved in I/Rc5 group when compared to I/R group and did not differ from the I/Rp group (p<0.05). MSTD, GECT, and JS were better in I/Rc5 than I/Rp which showed the natural course of I/R damage in testis (p<0.005). Caspase 3 positivity, as an apoptosis indicator, were significantly lower (p<0.05) in I/Rc5 group in comparison with I/R, I/Rc1, and I/Rp groups. CONCLUSION: The usage of colchicine as a complementary treatment after definitive surgery reduce early-onset ischemia-reperfusion damage and diminishes apoptosis.

Anticonvulsive and behavior modulating effects of sophoretin and rutoside.

INTRODUCTION: Seizures are the hallmarks of most types of epilepsies. Behavioral and cognitive impairments coincide with interictal periods even though it is not clear whether these impairments spring out of the seizure itself or accompanying sociopsychological burden of the disease. MATERIALS AND METHODS: In this study, we investigated behavioral and cognitive consequences of a single GABA receptor-related seizure in mice, and examined the potential anticonvulsive and behavior-modulating properties of sophoretin (quercetin) and rutoside (rutin). RESULTS: The study demonstrated that sophoretin and rutoside, common flavonoids of the human diet, delay the seizure onset and reduce the seizure stage. Moreover, they exerted an antidepressant-like effect, which was independent of the seizure. Neither treatments nor seizure altered recognition and spatial memory performances of the mice. CONCLUSIONS: Behavioral or cognitive disturbances that are evident in epileptic patients did not appear following a single seizure. In addition, we suggest that both sophoretin and rutoside successfully alleviate the seizure severity without interfering in the behavioral stability and cognitive performance. Hence, these flavonoids may be of use as adjuncts to the current treatment options.

Investigation of Therapeutic Effects of Erdosteine on Polycystic Ovary Syndrome in a Rat Model.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a serious endocrine disorder. In the present study, we investigated the therapeutic effects of erdosteine in letrozole-induced PCOS in rats. METHODS: Thirty-two Wistar albino female rats were grouped as control group (C), PCOS group (PCOS), PCOS-metformin group (PCOS+MET), and PCOS-erdosteine group (PCOS+Erd). PCOS was induced by administering letrozole; such rats presented with sex hormone disorder, abnormal estrous cycles determined by daily vaginal smear, large cystic follicles, and increasing fasting insulin levels. After induction of PCOS, metformin (500 mg/kg/day) and erdosteine (100 mg/kg/day) were given orally to the treatment groups for 30 days. Serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, circulating estrone (E1), estradiol (E2), testosterone, and androstenedione were evaluated. The ovaries were graded histologically. RESULTS: Weights of ovarian tissues (p < 0.05) and the number of atretic follicles (p < 0.001) and cystic follicles (p < 0.01) decreased in the PCOS+Erd group; the corpus luteum number was significantly higher in the PCOS+Erd group (p < 0.01) as compared with the PCOS group. Lipid parameters (total-C, LDL-C, and TG), E1 (estrone), E1/E2 ratio, testosterone, and androstenedione significantly decreased, while HDL-C and E2 (estradiol) significantly increased in the PCOS+Erd group as compared with the PCOS group. Moreover glucose, insulin, and HOMA-IR were reduced with treatment of erdosteine (p > 0.05, p < 0.001, and p < 0.001, respectively). CONCLUSION: It is suggested that erdosteine may be used in the treatment of PCOS as an alternative to metformin. It appears that our findings might be supported by clinical and molecular studies.

Detrimental effects of chia (Salvia hispanica L.) seeds on learning and memory in aluminum chloride­induced experimental Alzheimer's disease.

Polyphenols and omega­3 fatty acids are thought to have beneficial effects in Alzheimer's disease, the most common cause of dementia. Seeds of chia (Salvia hispanica L.) are highly rich in these nutrients, and thus, the present study investigated the effects of chia seeds on behavior and cognition in an aluminum­induced Alzheimer's disease model in rats. Experimental animals received chia supplementation either during the generation of the model (i.e., pretreatment) or after the model was established (i.e., treatment). A battery of behavioral and cognitive tests were performed, including open­field, elevated plus maze, Porsolt's forced swim, and Morris' water maze, to evaluate anxiety­ and depression­like behaviors, and learning and memory. Results showed that chia supplementation was ineffective against Alzheimer's­related anxiety, whereas depression­like behaviors were attenuated with both pretreatment and treatment. There was no improvement in learning and memory with chia treatment. Rather, cognitive performance in chia­pretreated animals was remarkably worse as compared to their non­treated disease­induced counterparts. Hippocampal concentrations of amyloid-ß42, amyloid precursor protein, and total tau protein were similarly increased in all disease­induced animals (despite chia supplementation), as compared to the controls. Based on these findings, chia supplementation during the progression of Alzheimer's disease may exacerbate the disease. Although the results presented here emerge from an experimental/preclinical study, we suggest cautious and careful use of chia, especially in early­stage Alzheimer's patients, until future research in different experimental settings is conducted.

Lecture attendance improves success in medical physiology.

The educators have underlined the importance of lecture attendance for decades. Nowadays, students have ample online educational sources, which began a debate on the necessity of in-class lectures. In the present study, we investigated the influence of lecture attendance on the exam success. To this aim, we adopted a novel approach and matched second-year medicine students' answers in three interim exams with the lectures related to those questions. Thereby, we were able to evaluate if attending lectures increases the chance of giving a correct answer to the exam question generated from the attended lecture. Furthermore, we examined students who had never taken the course before (first-time takers) and students who had failed and repeated the course (repeat takers) separately, since repeat takers may have attended a lecture previously. We found that first-time takers attended more lectures and gained higher total scores than repeat takers. Lecture-matched correct answers were significantly higher for attended lectures than for skipped lectures in all interim exams. Moreover, the correlation analyses revealed that the number of correct answers increases by lecture attendance in both first-time and repeat takers. These results indicate that in-class lectures still should be considered as an essential part of the medical physiology education, even in the internet era.

Systemic side effects of locally used oxymetazoline.

OBJECTIVES: The object of the study is to experimentally investigate the possible systemic side effects of Oxymetazoline including its nasal spray which has been in use for a long time both by the physicians and patients. There is no study in the literature to address the damages of oxymetazoline on the end organ. MATERIALS AND METHODS: The study conducted on 2 groups of rat. Group 1 (n = 8): Control; and Group 2 (n = 8): Oxymetazoline. During 4 week, the control group was applied with 2 drops of saline water on each nasal cavity 3 times a day and the other group was applied with 2 drops of oxymetazoline HCl 3 times a day. At the end of experiment, samples from mandible, parotid and tails of the rats were taken in 10% formalin for histopathological investigations. RESULTS: In histopathological experiments, when compared with the control group, the oxymetazoline group showed significant increase in many of the histopathological parameters (ischemic changes: P = 0.0001; congestion: P = 0.0006; arterial thrombosis: P = Ns; PNL accumulations: P = 0.001; necrosis: P = 0.0001; and ulceration: P = 0.014). The results of histopathologic tests on the samples taken from mandible and parotid gland, in comparison with the control group, showed no significant increase (focal inflammation: P = Ns; and lymphocyte aggregation: P = Ns). CONCLUSION: Due to the damage that the long-term use of nasal spray including oxymetazoline, it may cause injury on the end organ, which we revealed in our histopathological experiments. We believe that it's essential for the physicians to provide information on the side effects of the medicine to their patients who use for a long term.

Ameliorating effect of quercetin on acute pentylenetetrazole induced seizures in rats.

OBJECTIVE: The aim of the study to elicit effects of pure quercetin in pentylenetetrazole (PTZ) and picrotoxin induced seizures. MATERIALS AND METHODS: Each animal group was divided into six groups and composed of six rats. Rats were assigned to the following experiments and groups (G): (G1) PTZ 45 mg/kg + DMSO; (G2) PTZ 45 mg/kg + 5 mg/kg quercetin; (G3) PTZ 45 mg/kg + 10 mg/kg quercetin; (G4) PTZ 45 mg/kg + 20 mg/kg quercetin; (G5) PTZ 45 mg/kg + 40 mg/kg quercetin; (G6) Picrotoxin 5 mg/kg + DMSO; (G7) Picrotoxin 5 mg/kg + 10 mg/kg quercetin; (G8) Picrotoxin 5 mg/kg + 20 mg/kg quercetin. In all groups quercetin were injected 30 min before PTZ and picrotoxin applications. RESULTS: Compared to PTZ, quercetin significantly prolonged onset of the seizure in 10 mg/kg (P < 0.05) and reduced the seizure stage in 10 mg/kg quercetin injected group (P < 0.01). Compared to PTZ, quercetin also declined the generalized seizure duration at 10 mg/kg (P < 0.01) and 20 mg/kg (P < 0.05) doses. At the doses of 5 mg/kg and 40 mg/kg quercetin there were no significant changes in seizure parameters. Development of picrotoxin induced seizures is slower than in PTZ. Quercetin was found to be unable to prevent seizure in picrotoxin induced seizures. Surprisingly, quercetin also significantly reduced the onset of seizures at the dose of 20 mg/kg (P < 0.05). CONCLUSION: quercetin (at doses of 10 and 20 mg/kg i.p) prevented seizures in PTZ (45 mg/kg i.p) induced seizures. Especially, 10 mg/kg PTZ prolonged onset of seizures, reduced the seizure duration and seizure severity score in comparison with control group. At a higher (40 mg/kg) dose quercetin failed to prevent PTZ induced seizures. In addition 20 mg/kg quercetin significantly reduced the onset of seizures that suggest a preconvulsive effect. 20 mg/kg quercetin reduced the onset of picrotoxin induced seizures. In picrotoxin model, it may be claimed that quercetin at higher doses accelerate the epileptic activity owing to its antagonistic effect on GABAA. Further investigations are needed to explore the mechanisms of the antiepileptic and preconvulsant effects of quercetin.