Effect of vitamin C on histomorphometric changes of testis, epididymis, prostate, and seminal vesicle induced by acrylamide in rat.

Acrylamide (ACR) has adverse effects on the rat testis. This study aimed to assess the impact of ACR and vit C exposure on reproductive organs in rats. In this experimental study, 32 adult male rats were used. The animals were divided into 4 groups (n = 8): (1) control group, (2) ACR (10 mg/kg) group, (3) vit C (200 mg/kg), (4) ACR (10 mg/kg) + vit C (200 mg/kg) daily for 5 weeks by gavage. After the administration period, testis, prostate, seminal vesicle, and epididymis of animals are removed; after preparing tissue sections, the structural changes of the tissues are examined by stereology. Data were analyzed using one-way ANOVA followed by the Tukey test in SPSS software. A value of p ≤ 0.05 was considered significant. The testis weight, volume (mm3), and the mean Johnsen score showed a significant decrease in comparison with the control group and vit C-treated group. These parameters were increased in ACR + vit C group. The number of spermatogonia, spermatocyte, spermatid, and Sertoli and Leydig cells in ACR-treated group showed a significant decrease in comparison with the control and vit C-treated groups. The number of these cells was increased in the ACR + vit C group. Epithelium height and folding of prostate and seminal vesicle in the ACR-treated group were decreased. Epithelium lost its integrity. In the ACR + vit C group, histopathological changes were decreased. Seminal vesicle of ACR + vit C-treated group showed mild degeneration and rupture in epithelium integrity. The epididymis of ACR + vit C group also showed mild degeneration and rupture in epithelium integrity.

Antidepressant-like effect of endogenous SO2 on depression caused by chronic unpredictable mild stress.

Sulfur dioxide (SO2) is a toxic gas with harmful effects on various organs. However, recent studies have confirmed the protective effect of SO2 on ischemic heart disease, atherosclerosis, and lung infections. Therefore, the present study was designed to investigate the effect of endogenous SO2 on depression. The chronic unpredictable mild stress (CUMS) model was performed to cause depression. Depression-like behaviors in animals were determined using an open-field test, forced swimming test, and sucrose consumption. Animal spatial learning and memory were also assessed using the Morris water maze. Besides, the oxidative status of the hippocampus and serum corticosterone level were evaluated. A reduction in the tendency to consume sucrose, mobility, and curiosity, as well as learning and memory disorders were observed in CUMS animals. Depressed animals treated with SO2 revealed a significant improvement in behavioral and cognitive functions. SO2 also reduced neuronal damage and lipid peroxidation of the hippocampus and serum corticosterone level in the CUMS group. Various shreds of evidence support a mutual relationship between inflammation and depression; also, growing studies show the role of oxidative stress in the pathogenesis of mood-related disorders such as depression. This study indicated that increased hippocampal malondialdehyde (MDA) and serum corticosterone levels can be due to the existence of oxidative stress and possible activation of inflammatory processes. SO2 donors diminished MDA and corticosterone levels in depressed animals. According to the study results, SO2 may be able to reduce tissue damage and eventually behavioral disorders caused by depression by lowering oxidative stress and inflammation.

Cyanocobalamin improves memory impairment via inhibition of necrosis and apoptosis of hippocampal cell death after transient global ischemia/reperfusion.

OBJECTIVES: Brain ischemia/reperfusion (I/R) causes irreversible damage, particularly in the hippocampus. Cyanocobalamin (CNCbl) is known to be crucial for the proper operation of the nervous system. Vitamin B12 has been demonstrated to exert antioxidant effects via direct and indirect mechanisms. It can also protect cortical neurons against glutamate cytotoxicity. This research was conducted to examine CNCbl protection against neuronal cell death in the rat hippocampal region following transient cerebral ischemia. MATERIALS AND METHODS: In this experiment, 48 male Wistar rats were selected, which were randomly divided into four groups (n=12 in each group): sham, ischemia/reperfusion, ischemia/reperfusion + CNCbl 200 and 400 (µg/kg). By occlusion of both common carotids, ischemia induction was performed within 20 min. CNCbl at the doses of 200 and 400 µg/kg was injected (IP) at the start of the reperfusion, 24 and 48 hr following reperfusion. The spatial memory was assessed 7 days following ischemia through the Morris water maze test. Antioxidant enzymes, apoptosis, and necrosis were measured after behavioral tests. RESULTS: CNCbl significantly improved spatial memory impairments (P<0.05), also CNCbl therapy significantly increased both glutathione (P<0.01) and superoxide dismutase (P<0.05) and reduced malondialdehyde (P<0.01) and TNF-α (P<0.05) in comparison with the ischemia group. In addition, CNCbl significantly decreased both apoptosis and necrosis in the hippocampus CA1 (P<0.01). CONCLUSION: CNCbl improves memory impairment following ischemia injury by decreasing neuronal cell death via its antioxidant properties.

The effects of caffeine on ovarian tissue in rats.

Caffeine consumption increases during early adulthood, which has adverse effects on the reproductive system. This study aimed to assess the impact of embryonic caffeine exposure on rat ovary in adulthood. Female Wistar rats (240-270 g) were divided into 5 groups (n = 7): experimental groups were exposed to 26, 45, 100, and 150 mg/kg of caffeine via drinking water during pregnancy and the control group only received drinking water. The ovaries of the offspring were taken out on days 7, 14, 28, 60, 90, and 120 of postnatal development, and then, they were fixed in 10% formaldehyde solution. Ovarian follicles were studied using stereological methods, and data were analyzed using one-way ANOVA followed by the Tukey test in SPSS software. A value of p < 0.05 was considered significant. The body weight, the weight of the ovaries, the ovarian volume, and the number of primordial follicles decreased significantly (p < 0.05) in 45 and 100 mg/kg, and (p < 0.001) in 150 mg/kg caffeine-treated groups at all stages of postnatal development. Significant decreases were observed in the number of primary and secondary follicles in 45 and 100 mg/kg (p < 0.05) and (p < 0.001) in 150 mg/kg caffeine-treated groups on days 7, 14, 28, and 60 compared to the control group. The number of Graafian follicles also decreased significantly (p < 0.001) in 45, 100, and 150 mg/kg caffeine-treated groups on days 14 and 28. Moreover, the mean volume of the oocyte in Graafian follicles reduced considerably in 45, 100, and 150 mg/kg caffeine-treated groups compared to other groups (p < 0.05). The thickness of the zona pellucida (ZP) in the secondary follicles (p < 0.02) and Graafian follicles (p < 0.05) showed a significant reduction in 100 and 150 mg/kg caffeine-treated groups on the 14th, 28th, and 60th days. In conclusion, high-dose caffeine consumption during gestation affects all stages of ovarian follicle development in rat offspring.

Effect of myricetin on the gene expressions of NOX3, TGF-ß1, prestin, and HSP-70 and anti-oxidant activity in the cochlea of noise-exposed rats.

OBJECTIVES: Noise-induced hearing loss is one of the most common occupational diseases in industrialized countries and can be affected by various environmental and genetic factors. This study was designed to examine the effect of myricetin in preventing this disorder. MATERIALS AND METHODS: Twenty-one Wistar rats were randomly divided into five groups: Non-exposed, noise exposure only, noise exposure with vehicle, noise exposure with myricetin 5 mg/Kg, and noise exposure with myricetin 10 mg/kg. All animals were sacrificed after last noise exposure. The left cochlea was dissected from each rat. It was used for mRNA expression analysis (NOX3, TGF-ß1, prestin, and HSP-70). Blood samples were collected to assess superoxide dismutase (SOD) activity, 1, 1 diphenyl picrylhydrazyl (DPPH), and malondialdehyde (MDA) measurements. RESULTS: Real time-PCR assay revealed that noise decreased NOX3 and increased TGF-ß1, prestin, and HSP-70 gene expressions. Administration of myricetin at the dose of 5 mg/kg, but not at 10 mg/kg, significantly reversed these changes. Noise also increased MDA levels and decreased SOD and DPPH scavenging activities. Myricetin at the doses of 5 and 10 mg/kg also reversed these changes. CONCLUSION: The findings of this study showed that myricetin at the dose of 5 mg/Kg was able to reverse noise-induced abnormalities in gene expression and oxidant/anti-oxidant balance. It is a possibility that myricetin via enhancement of anti-oxidant activity induced these effects.

Carvacrol reduces hippocampal cell death and improves learning and memory deficits following lead-induced neurotoxicity via antioxidant activity.

Carvacrol is a monoterpene with neuroprotective effects in several animal models of neurodegeneration, including epilepsy, ischemia, and traumatic neuronal events. In this study, we aimed to examine the effects of carvacrol on neurodegeneration induced by lead acetate in rats. A total of 50 male Wistar rats were divided into five equal groups. The control group received drinking water, while the neurotoxic group was exposed to 500 ppm of lead acetate in drinking water for 40 days. The three remaining groups, which were also exposed to 500 ppm of lead acetate, received carvacrol at doses of 25, 50, and 100 mg/kg orally for 40 days. The Morris water maze test was employed to examine spatial learning and memory. Pathological damage to the hippocampus was determined by Nissl staining. The level of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were detected using biochemical analysis and the free radical scavenging activity as evaluated by the DPPH test. Administration of carvacrol significantly restored learning and memory impairment induced by lead acetate. Moreover, carvacrol ameliorated neurodegeneration, antioxidative capacity, and lipid peroxidation in the hippocampus of rats exposed to lead. The present results provide a rationale for the inhibitory role of carvacrol in the attenuation of lead-induced neurotoxicity.

Effect of endogenous sulfur dioxide on spatial learning and memory and hippocampal damages in the experimental model of chronic cerebral hypoperfusion.

Background The vascular changes due to cerebrovascular damage, especially on the capillaries, play a vital role in causing vascular dementia. Increasing oxidative stress can lead to tissue damage while reducing brain blood flow. The use of factors reducing the oxidative stress level can decrease the brain damages. Sulfur dioxide (SO2) is one of the most important air pollutants that lead to the development of severe brain damage in large quantities. However, studies have recently confirmed the protective effect of SO2 in cardiac ischemic injury, atherosclerosis and pulmonary infections. Methods The permanent bilateral common carotid artery occlusion (BCAO) method was used to induce chronic cerebral hypoperfusion (CCH). Two treatment groups of SO2 were studied. The animal cognitive performance was evaluated using the Morris water maze. Hippocampal tissue damage was examined after 2 months of BCAO. In the biochemical analysis, the activity of catalase and lipid peroxidation of the hippocampus was studied. Results Neuronal damage in hippocampus, as well as cognitive impairment in ischemia groups treated with SO2 showed a significant improvement. Catalase activity was also significantly increased in the hippocampus of treated groups. Conclusions According to the results, SO2 is likely to be effective in reducing the CCH-caused damages by increasing the antioxidant capacity of the hippocampus.

Carvacrol suppresses learning and memory dysfunction and hippocampal damages caused by chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is a common phenomenon in many neurological diseases such as vascular dementia and Alzheimer's disease. Several drugs have been investigated to prevent and treat the CCH. The carvacrol (CAR) has been shown to have beneficial effects on various neurodegenerative and neuropsychiatric disorders. Accordingly, the present study was designed to evaluate the effect of CAR on neuronal damages in hippocampus in a well-defined model for CCH. Forty-eight male Wistar rats were equally divided into four groups of sham (A), CCH (B), CCH+ CAR 25, and 50 mg/kg/daily (C and D). The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce CCH model. Cognitive function was evaluated by Morris water maze test. Morphological changes of hippocampus were assessed using Nissl staining. Free radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Moreover, catalase (CAT) and superoxide dismutase (SOD) activities and lipid peroxidation levels were measured using biochemical analysis. CAR significantly improved the spatial learning and memory deficits assessed using the Morris water maze test. CAR also significantly attenuated neuronal necrosis as well as malondialdehyde (MDA) and elevated the levels of SOD and CAT activity in the hippocampus. The results indicate that CAR produces significant neuroprotective effects on neuronal damages induced by CCH. Protective effect of CAR may be mediated by antioxidative effect of this drug.

Effect of berberine chloride on caspase-3 dependent apoptosis and antioxidant capacity in the hippocampus of the chronic cerebral hypoperfusion rat model.

OBJECTIVES: The main goal of the current research was to examine the effects of Berberine (BBR) on apoptotic signaling and hippocampal oxidative stress induced by common carotid artery occlusion. MATERIALS AND METHODS: Chronic cerebral hypoperfusion (CCH) model was created by occluding the two common carotid arteries (two-vessel occlusion [2VO]) permanently. BBR (50 and 100 mg/kg/daily) was intra-gastrically administered to ischemic rats. Neuronal survival was evaluated by Nissl staining. The levels of malondialdehyde (MDA) and antioxidant enzymes, including catalase (CAT) and superoxide dismutase (SOD), along with the activities of caspase 3 were estimated in the hippocampus 2 month after treating the rats with 2VO. RESULTS: According to findings of the present research, the BBR therapy inhibited the neuro-degeneration of hippocampus. BBR also significantly decreased the amount of MDA and activity of caspase 3 in the hippocampus. Furthermore, the administration of BBR alleviated the lowered activities of SOD and CAT after 2VO surgery. CONCLUSION: The antioxidant and antiapoptotic properties of BBR might play important roles in improving functional outcomes and might have significant neuroprotective effects on the CCH damage.

Sulfur dioxide reduces hippocampal cell death and improves learning and memory deficits in a rat model of transient global ischemia/reperfusion.

OBJECTIVES: According to recent the findings, sulfur dioxide (SO2) is produced by the cardiovascular system, influencing some major biological processes. Based on previous research, SO2 exhibits antioxidant effects and inhibits apoptosis following cardiac ischemia/reperfusion. Therefore, the objective of the current study was to examine the neuroprotective impact of SO2 following global cerebral ischemia/reperfusion (I/R). MATERIALS AND METHODS: Forty-eight male Wistar rats that weighed 260-300 g, were randomly allocated into 4 groups: sham group (n=12), I/R group (n=12), and I/R+SO2 groups (NaHSO3 and Na2SO3; 1:3 ratio; 5 and 10 µg/kg, respectively; for 3 days, n=12). Cerebral ischemia model was prepared by occlusion of both common carotid arteries for 20 min. Saline as a vehicle and SO2 donor at doses 5 µg/kg (intraperitoneally) were injected for 3 days after reperfusion. Four days after ischemia, the passive avoidance memory test was carried out in four groups, and after behavioral assessment, necrosis, apoptosis, and antioxidant enzyme analysis were carried out. RESULTS: O2 treatment could significantly improve memory impairments in rats with cerebral ischemia/reperfusion (I/R) (P<0.05). An increase in both superoxide dismutase and glutathione and a reduction in malondialdehyde were reported in the SO2 group versus the ischemic group (P<0.05). Moreover, SO2 could significantly decrease necrotic and apoptotic cells in the CA1 region (P<0.01). CONCLUSION: According to the findings, SO2 exerts significant neuroprotective effects on cerebral I/R due to its antioxidant activity.

Effect of Maternal Stress Prior to Conception on Hippocampal BDNF Signaling in Rat Offspring.

Environmental factors, especially stress, can remain pervasive effects across the lifespan. Traumatic experiences are risk factors for the behavioral and emotional disorders. Since brain-derived neurotrophic factor (BDNF) is the important regulator of neural survival, development, and its genetic and epigenetic alterations which have been linked with several neuropsychiatric disorders, the present study investigated the effect of maternal adulthood stress on molecular changes of BDNF and tyrosine kinase-coupled receptor (TrkB) in the hippocampus of 30-day-old offspring. To induce stress, we employed a repeated forced swimming model for female rats across 21 days. Then, they were divided into two parental breeding groups: stressed mother (SM) and non-stressed mother (NSM) or control group. Anxiety-like behavior was tested in adult female rats and 30-day-old pups by using the elevated plus maze (EPM). The level of serum corticosterone was also measured by ELISA. BDNF and TrkB gene methylation and protein expression in the hippocampus were detected using real-time PCR and Western blotting in all groups. Thirty-day-old male and female pups from SM groups had a significantly more serum corticosterone concentration, DNA methylation levels of BDNF and TrKB, and lower expression of these genes compared to pups from the control groups. Also, male pups from stressed mother exhibited significant anxiety-like behavior compared to male pups from the control mothers. These findings suggest that molecular changes formed by maternal stress experience even before conception persist to the next generation and will negatively influence on phenotypes of offspring.

Increased phosphorylation of mTOR is involved in remote ischemic preconditioning of hippocampus in mice.

Different signaling pathways are involved in tissue protection against ischemia reperfusion (IR) injury, among them mammalian target of rapamycin (mTOR) and related pathways have been examined in many recent studies. Present study evaluated the role of mTOR in remote ischemic preconditioning (RIPC) of hippocampus. Renal ischemia was induced (3 cycles of 5min occlusion and 5min reperfusion of unilateral renal artery) 24h before global brain ischemia (20min bilateral common carotid artery occlusion). Saline or rapamycin (mTOR inhibitor; 5mg/kg, i.p.) was injected 30min before RIPC. mTOR and phosphorylated mTOR (p-mTOR) expression, superoxide dismutase (SOD) activity and retention trial of passive avoidance test were determined 24h after global ischemia. Apoptosis and neuronal cell density were assessed 72h after hippocampal ischemia. RIPC decreased apoptosis (p<0.05 vs. IR), improved memory (p<0.05 vs. IR), and augmented p-mTOR expression and SOD activity after hippocampal ischemia (p<0.05 vs. IR). Rapamycin abolished all protective effects of RIPC (p<0.05 vs. RIPC+IR) suggesting a role for mTOR in RIPC induced hippocampal protection.

Parents' adulthood stress induces behavioral and hormonal alterations in male rat offspring.

Exposure to stress can influence hypothalamo-pituitary-adrenal (HPA) axis in mammals and impair their behavioral/hormonal development. Stress during fetal or early life may have wide range effects on the offspring phenotype in rodents. Since the role of parents' adulthood stress before mating is not fully understood yet, we investigated the effects of parents' adulthood stress on behavioral and hormonal parameters in 10- and 30-day-old male offspring. To induce stress in the adult male and female rats, a repeated forced swimming paradigm was employed daily over the course of 21 days. Then, they were categorized into four parental breeding groups: stressed parents (SP), stressed mother (SM), stressed father (SF) and non-stressed parents (NSP). Anxiety-like behavior was tested in adult rats and 30-day-old male pups, using the elevated plus maze (EPM). The level of serum corticosterone was measured by ELISA in all groups. Stressed adult rats showed enhanced serum corticosterone concentration and anxiety-like behavior. Serum corticosterone level of the 10- and 30-day-old pups of the SP, SM and SF groups was significantly higher than pups from the non-stressed group. Furthermore, 30-day-old pups of the SP, SM and SF groups had lower time spent in the open arms compared to the control group, but stress had no significant effects on the percent of entries into the open arms. In addition, serum corticosterone level in 30-day-old pups were raised by a stressed mother was markedly more than 10-day-old pups. These findings revealed that parents' adulthood stress have negative impacts on behavioral and hormonal responses of their male offspring.