Radioprotective effect of Cerebrolysin in the Rat's Brain Tissues.

AIM: The aim of this study is to evaluate radioprotective effects of Cerebrolysin (CBL) in rats' brain tissues after local irradiation. BACKGROUND: CBL has demonstrated antioxidant, anti-inflammatory, and tissue repair properties. In this study, the radioprotective effects of CBL in the brain tissues of rats after Irradiation (IR) (50 mg/ kg) were evaluated. OBJECTIVE: The levels of different oxidative stress markers, including malondialdehyde (MDA), nitric oxide (NO), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were examined after treatment with radiation and CBL. METHODS: First, 20 male adult Wistar rats weighing 180-200 g were used. The animals were exposed to a single fraction of 15Gy using a linear accelerator unit at a dose rate of 200 cGy/mine. In this study, to check the amount of oxidative stress following the IR, the level of four markers MDA, NO, GPx, CAT, and SOD were examined and measured using the spectrophotometric method and purchased kits. RESULTS: The results showed that compared to the IR group, the administration of CBL increases the levels of GPX and SOD significantly (p < 0.05). CONCLUSION: Our finding suggests that CBL has radioprotective effects on the brain by enhancing antioxidant defense mechanisms.

Effect of risperidone on morphine-induced conditioned place preference and dopamine receptor D2 gene expression in male rat hippocampus.

BACKGROUND: Previous studies suggest the possible effect of risperidone on brain reward system and D1 and D2 dopamine receptors' involvement in morphine-induced conditioned place preference (CPP). AIMS: The present study was designed to investigate the effect of risperidone as an atypical antipsychotic drug on morphine-induced CPP and D2-like dopamine receptor gene expression in rat. MATERIALS AND METHODS: An unbiased CPP paradigm was used to study the effect of risperidone. Intraperitoneal (i.p.) injection of risperidone (1, 2, and 4 mg/kg) was performed 30 min before the morphine (10 mg/kg, i.p.) injection and just after the rat was placed in the CPP box. The open field test was used to assay the locomotor activity of animal. The gene expression of D2 dopamine receptor in hippocampus was measured by real-time PCR technique. The hippocampi of rats were also used for histology evaluation. RESULTS: Morphine-produced (10 mg/kg) CPP and morphine-induced CPP were reversed only by the administration of a low dose of risperidone (1 mg/kg). Low dose of risperidone (1 mg/kg) showed no effect on locomotor activity but a higher dose of risperidone (2 and 4 mg/kg) decreased locomotor activity. Real-time PCR data analysis revealed that the gene expression of D2 dopamine receptor had significant difference between morphine and a 1 mg/kg dose of risperidone. Moreover, in histological evaluation, apoptosis was observed in the morphine group, whereas there was no evidence of apoptosis in the risperidone-treated groups. CONCLUSION: Our results suggest that risperidone (1 mg/kg) reverses the morphine-induced CPP and may reduce the rewarding properties of morphine. It is also demonstrated that risperidone decreases the expression of D2 receptor in rat hippocampus. Therefore, risperidone can be considered potential adjunct therapy in morphine dependence.

The effect of vitamin D on morphine preference in rats: Possible biochemical and DRD2-GDNF signaling.

INTRODUCTION: Despite half a century of research on vitamin D (Vit. D), its link to substance abuse and dependence has only been discussed in recent decades. Evidence also shows the involvement of Vit. D in the evolution of dopaminergic neurons in the nucleus accumbens, an increase in the expression of tyrosine hydroxylase, and the regulation of dopaminergic processes. The novel idea for this work is taken from a hypothesis given about the effectiveness of Vit. D on dopamine signaling pathway. It is therefore presumed that Vit. D can be considered an effective therapeutic approach for narcotic addiction and substance abuse. METHODS: The animals were assigned into six groups (control, vehicle, Morphine [Mor.], and Vit. D [250, 500, and 1000 IU/kg, i.p.]). Following each conditioning session in a conditioned place preference (CPP) model, the animals received Vit. D. Afterward, the locomotor activity of the animals was assessed using open-field apparatus. Malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), superoxide dismutase (SOD), thiol, and total antioxidant capacity (TAC) were measured in the brain. The relative DRD2 and GDNF expressions (%) were also measured in the hippocampus. RESULTS: Vit. D administration after Mor. caused a significant increase in the place preference index in the acquisition phase (p < .05). Vit. D altered the oxidation/antioxidation profiles (CAT, SOD, MDA, NO, TAC, and Thiol). Vit. D was more effective than Mor. in the expression of GDNF (p < .0001); however, in the expression of DRD2, this was only the case for 1000 IU Vit. D (p < .0001). CONCLUSIONS: Considering the increased place preference index induced by Mor., it can be concluded that Vit. D interacts via the oxidative pathway and DRD2-GDNF signaling to potentiate the Mor. effect.

L-Lysine Ameliorates Diabetic Nephropathy in Rats with Streptozotocin-Induced Diabetes Mellitus.

Introduction: Diabetic nephropathy is one of the leading causes of end-stage renal disease worldwide. Uncontrolled hyperglycemia and subsequent production of glycation end-products activate the paths which lead to diabetic nephropathy. The aim of this study was to assess the effects of L-lysine on antioxidant capacity, biochemical factors, kidney function, HSP70 level, and the expression of the TGFß, VEGF, and RAGE genes in rats with streptozocin-induced diabetes mellitus. Methods: Thirty-two male Wistar rats were randomly allocated to four eight-rat groups, namely, a healthy group, a diabetic group treated with vehicle (DM + vehicle), a diabetic group treated with L-lysine (DM + Lys), and a healthy group treated with L-lysine (healthy + Lys). Rats in the DM + Lys and the healthy + Lys groups were treated with L-lysine 0.15%. The levels of fasting blood glucose, insulin, HbA1C, advanced glycation end-products (AGEs), lipid profile, serum creatinine, blood urea nitrogen, glomerular filtration rate, urine microalbumin, oxidative stress parameters, kidney histology and morphology, and TGFß, VEGF, and RAGE gene expressions were assessed. Findings. An eight-week treatment with L-lysine significantly reduced the levels of fasting blood glucose, AGEs, kidney function parameters, oxidative stress parameters, lipid profile, and the TGFß, VEGF, and RAGE gene expression and significantly increased the levels of serum insulin and tissue HSP70. Conclusion: Treatment with L-lysine seems to slow down the progression of diabetic nephropathy.

Cardioprotective effects of cerebrolysin on the lesion severity and inflammatory factors in a rat model of isoproterenol-induced myocardial injury.

BACKGROUND: Myocardial injury (MI) is an important heart condition and a major cause of morbidity and mortality worldwide. The current study was designed to investigate the cardioprotective effects of cerebrolysin (CLY) on the lesion severity and inflammatory factors in male rats using isoproterenol (ISO)-induced MI model. METHODS: MI in rats was induced by injecting ISO (100 mg/kg) subcutaneously (sc) on the first 2 days. Then, CLY (5 ml/kg) was injected intraperitoneally (ip) post-treatment for 7 days. On the 3rd day, creatine phosphokinase (CK-MB) and cardiac troponin I (cTnI) levels in serum and, on the 10th day, the TNF-α and IL6 levels in serum and heart tissue were measured by enzyme-linked immunosorbent assay (ELISA). Finally, the heart of each rat was dissected out and stained for histopathological examination. RESULTS: On the 3rd day, the serum CK-MB and cTnI levels in the ISO and CLY + ISO groups were significantly increased compared with that in the control and CLY + Sal groups. One week after the induction of MI, ISO administration showed a significant increase in the serum level of TNF-α in the ISO group compared with that in the control and CLY + Sal groups. Also, our findings showed only a moderate reduction in inflammatory cell infiltration and extent of edema following CLY treatment in the CLY + ISO group. Also, CLY induced vascular proliferation in the heart tissue. CONCLUSIONS: We conclude that the severity of pathological changes induced by ISO in MI (e.g. inflammation and edema) can be limited by CLY treatment.

Ameliorative effects of cerebrolysin against isoproterenol-induced myocardial injury in male rats.

AIMS: Myocardial injury (MI) is the principal cause of death from cardiovascular disease (CVD). The present study was conducted to investigate the ameliorative and antioxidant effects of cerebrolysin (CBL) on isoproterenol-induced MI in rats. METHODS: MI was induced in the rats by subcutaneously injecting 100 mg/kg of isoproterenol (ISO) in the first two days. The serum levels of creatine phosphokinase (CK-MB) and cardiac troponin I (cTnI) were measured on the third day to confirm MI. The post-treatment involved intraperitoneally injecting 5 ml/kg of CBL for 7 days. Nitric oxide (NO), malondialdehyde (MDA) in the heart tissue and catalase (CAT) and serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured on the 10th day using the enzyme-linked immunosorbent assay (ELISA). Histopathological examinations of the heart tissue were also performed. FINDINGS: The present results suggested significant increases in CK-MB, cTnI, MDA and NO. A significant decrease was also observed in the ISO-treated rats in certain antioxidant enzymes, including CAT and GPX. CBL administration showed a significant ameliorative increase against the oxidative ISO-induced damage. Moreover, the histopathological findings showed lower levels of the infiltration of inflammatory cells and edema and vascular proliferation in the CBL-treated rats. SIGNIFICANCE: The present histopathological and biochemical findings attributed antioxidant properties to CBL in the rat myocardium and suggested protective effects on ISO-induced MI.