Potential preventive and therapeutic effects of glutathione supplementation in experimental colitis

The aim of this study was to assess the potential preventive and therapeutic effects of glurathione [GSH] on inflammatory bowel diseases [IBD] and to evaluate the use of fecal calprotectin [FC] and fecal lactoferrjn [Lf] as a non-invasive diagnostic marker of IBD. Forty albino rats were divided into four groups; group I: control group; group II: acetic acid induced colitis group, group III: after colitis induction, rats were treated with glutathione for one week [50 mg/kg, i.p.] and group IV: before the induction of colitis, rats were given a preventive dose of glutathione [200 mg/kg, i.p]. At the end of experimental period, rats were sacrificed, fecal calprotectin and lactoferrin were assessed in the different groups, the level of antioxidants in the intestine was evaluated and the severity of inflammation was histopathologically scored. Intestinal glutathione level was decreased significantly after colitis induction, however, it was significantly high in the prevention group. There was significant reduction in the antioxidant enzymes after colitis induction. However, glutathione prevention was associated with higher antioxidant enzymes compared to treatment. Various histopathological changes as inflammation, ulceration and dysplasia were detected after colitis induction and in rats treated with glutathione, however, rats supplemented with glutathione as prevention showed no ulceration and mild inflammation. In addition, colitis induction was associated with significant increase in the colonic level of FC and Lf which was significantly reduced with glutathione prevention. Glutathione prevention appeared to be beneficial for the acute stage of IBD than glurathione treatment. Moreover, intestinal antioxidant enzymes were correlated negatively with FC level. FC and Lf can be used as non-invasive and simple marker for diagnosis of IBD

Role of oxytocin in the stress response in male and female rats

In addition to its role in reproduction, oxytocin [OT] has central actions modulating behavioural and hypothalamic-pituitary-adrenal axis responses during stress. This study was designed to evaluate the effect of endogenous and exogenous oxytocin administered as an intranasal inhalation on adrenocorticotrophic hormone [ACTH] and corticosterone level in the serum of male and female rats after exposure to stress; to evidence whether intranasal inhalation of oxytocin is associated with increase in its level in the cerebrospinal fluid [CSF]; and finally to assess any possible relation between the level of oxytocin and the levels of sex steroids during stress. This study was carried out on 10 male and 10 female adult rats; which were exposed to the forced swimming stress test with and without prior intranasal oxytocin inhalation. Thereafter, their anxiety behaviour was assessed by the elevated plus maze test. Blood and CSF samples were withdrawn before exposure to stress as well as after stress with and without oxytocin inhalation and were used for estimation of oxytocin level in the CSF, serum level of ACTH, corticosterone, estradiol and testosterone by enzyme immunoassay. The present study revealed a significant increase of CSF oxytocin after exposure to forced swimming stress test in both sexes; female rats however, exhibited more increase in oxytocin level. Exposure to stress was also associated with significant increase in serum level of ACTH and corticosterone in both sexes, female rats moreover, had lower level of these hormones compared to male rats. Oxytocin treatment was associated with significant increase in oxytocin level in CSF as well as reduction in the serum level of ACTH and corticosterone. With oxytocin treatment, a clear anxiolytic effect in animals was found as shown by the observations from the elevated plus-maze. A Positive significant correlation was found between serum estradiol and CSF oxytocin level in female rats, whereas, no significant correlation was noticed between serum testosterone level and CSF oxytocin level in male rats after exposure to stress. In conclusion, intranasal OT inhalation was associated with a significant increase in its CSE level; such central oxytocin can modulate hypothalamic-pituitary-adrenal [HPA] axis response in male and female rats by exerting inhibitory effect on ACTH and subsequently corticosterone secretion. Due to its anti-stress property, oxytocin can be used for psychotherapeutic intervention and treatment of numerous psychiatric illnesses. Although the central action of OT are generally inhibitory, our study suggested that circulating level of estrogen and not testosterone plays an important role modulating the effect of OT on HPA axis responsiveness to stress

Sex-specific p38 MAP kinase activation in myocardial ischemia reperfusion injury in dogs

Very little information exists concerning the influence of sex on the response of the myocardium itself to an acute insult such as ischemia-reperfusion [I/R]. It was suggested that differences in the activation of p38 may mediate the sex-related difference in myocardial signaling after I-R which may contribute to the lower incidence of cardiac complications in females after myocardial ischemia. To evaluate the effect of sex hormones on the activation of p38 MAP kinase in a canine model of ischemia reperfusion injury. This study was conducted on 42 adult dogs of both sexes, they were classified into three groups. The first group [group I] contained 14 male dogs, the second group [group II] included 14 cycling female dogs and the third one [group III] consisted of 14 female dogs which were ovariectomized 3 weeks prior to experiment. Each group was subdivided randomly into 2 equal subgroups, I/R group [n=7] and control group [n=7]. The myocardial I/R model included anesthesized open-chest dogs after 25 minutes occlusion of the left anterior descending coronary artery [LAD] and subsequent reperfusion. Myocardial p38 MAPK and TNF-alpha and serum estrogen as well as testosterone were measured. The present study revealed decreased levels of p38 and TNF- alpha levels in the hearts of female dogs compared to male dogs and ovariectomized females subjected to the same I/R injury, suggesting that sex differences may exist in the p38 MAPK signaling pathway and cytokine response. Our findings indicate that sex difference exists in the myocardial response to acute I/R, where females dogs showed some degree of myocardial protection than males and ovariectomized females. Endogenous estrogen may be partly responsible for this cardioprotective effect by lowering p38 MAPK activation and subsequent decrease in TNF-alpha production and this benificial effect is lost in ovariectomized females. In addition, the study confirmed the deleterious effects of testosterone on myocardium through activation ofp38 MAPK and the resulting increase in TNF- alpha production

Effect of estrogen and N-acetyl cystein on bone remodeling and bone cytokine osteoprotegrin in ovarectomized rats

Osteoporosis is one of the most common metabolic bone diseases which is characterized by loss of bone mass and predominantly affects menopausal women due to the loss of estrogen. Although the link between estrogen deficiency and bone loss is well established, the mechanisms through which estrogen deficiency stimulates bone resorption and impairs bone formation remain controversial. Estrogen deficiency may lead to osteoporosis by decreasing the production of osteoprotegrin [OPG], one of the important local regulators of bone turnover or by down regulating antioxidant pathways. We investigated the impact of estrogen deficiency [induced by ovariectomy] on bone cytokine osteoprotegerin and the process of bone remodeling. Also, we compared between the effect of estrogen replacement therapy and thiol antioxidant [NAC] supplementation in the protection against bone loss produced by estrogen deficiency. This study was carried out on fourty female Wistar rats, and divided into two main groups: normal control rats [n=10] and ovariectomized rats [n=30]. The control group was sham operated and received a weekly subcutaneous injection of a vehicle [100 micro L sesame oil]. The ovarectomized group was subjected to ovariectomy and was further subdivided into 3 subgroups; a non-treated group, 17-beta estradiol injected group and N- acetyl cystein [NAC] injected group. At the end of the experimental period, blood samples were collected from all experimental rats for measuring: serum alkaline phosphatase, serum osteocalcin and serum estradiol. Urine samples were also collected for measuring: urine hydroxyproline and urinary calcium excretion. After the rats were sacrificed, one femur from each rat was weighted and homogenized for the estimation of OPG content. In ovariectomized group there was a significant decrease in the serum estradiol level and a significant increase in markers of bone resorption [urinary hydroxyproline and urinary calcium excretion] with a significant but insufficient increase in the markers of bone formation [serum alkaline phosphatase as well as serum osteocalcin] which cause a state of negative remodeling balance. Moreover, there was a significant decrease in bone OPG level as compared to the normal control group. All these effects were reversed in the 17-beta estradiol treated ovariectomized group. In addition, the markers of bone resorption and formation, as well as the OPG level were corrected after administration of NAC in ovariectomized rats. Estrogen deficiency can lead to osteoporosis through reduction of OPG level and increasing in the reactive oxygen species [ROS]. 17-beta estradiol administration leads to increased concentrations of OPG, which inhibits osteoclastogenesis. Also administration of NAC prevents the occurrence of high bone turnover in ovariectomized rats. This effect was suggested to be due to either increase the levels of SOD and GPx which are known to be decreased in ovariectomized rats or through the increased level of OPG by unknown signaling mechanism. Thus it is suggested that NAC can be used in the prevention and treatment of osteoporosis in postmenopausal women either alone or in combination with small doses of estrogen

Fecal calprotectin, novel index for assessing the pathophysiological mechanisms of inflammatory bowel disease in rats treated by glutathione

In this study, the role of fecal calprotectin [FC] as a recent non-invasive diagnostic aid of inflammatory bowel disease [IBD] was evaluated and the effect of glutathione as a preventive and therapeutic factor in acetic acid induced colitis has been studied. Forty albino rats were divided into four groups; group I: acetic acid induced colitis group. Group II: before the induction of colitis, rats were given a preventive dose of glutathione [200 mg/kg, i.p]. Group III: after colitis induction rats were treated with glutathione for one week [50 mg/kg,i.p.]. Group IV: control group. At the end of experimental period, rats were sacrificed and fecal caiprotectin was assessed in the different groups, the level of antioxidant system in the intestine was evaluated and the severity of inflammation was histopathologically scored. Colitis induction was associated with significant increase in the colonic level of FC, which was significantly reduced with glutathione prevention. Glutathione level was decreased significantly in the intestine after colitis induction, however, it was significantly high in the prevention 'group. There was significant reduction in the antioxidant enzyme system after colitis induction. However, glutathione prevention was associated with higher antioxidant enzymes compared to treatment. Various histopathological changes as inflammation, ulceration and dysplasia were detected after colitis induction, group III, however, showed no ulceration and mild inflammation. Fecal caiprotectin can be used as a non-invasive and early marker for IBD. Glutathione prevention appeared to be beneficial for the acute stage of IBD than glutathione treatment. Moreover, intestinal antioxidant enzymes were correlated negatively with FC level

possible role of visceral adiposity in development of pro-atherogenic lipid profile in normal overweight young Egyptian female adults [a possible involvement of adiponectin and leptin]

The metabolic abnormalities that often co-exist with overweight and obesity appear to be mediated largely by visceral fat accumulation. Visceral fat is very different from the subcutaneous fat, and may be responsible for pro-atherogenic lipid profile in apparently healthy people. to examine the influence of visceral fat and "not obesity" on the lipid profile. In addition, to test the relation between adipocytokines [leptin and adiponectin] and lipid profile in overweight young healthy Egyptian adult females. Forty healthy young overweight females participated in this prospective cohort study, their age ranged from 19-23 Y, and their body mass index [BMI] ranged from 25-30 Kg/rn2. All the participants were completely healthy with no history of thyroid dysfunction; diabetes; or cardiovascular, renal, or liver dysfunction. No participant had taken medication for at least 3 months before the study, and none were dieting or smoking. The anthropometric measurements were made be the same observer in the physiology laboratory, Alexandria University, they induced: height, weight, body mass index [BMI], waist, hip circumference and waist hip ratio [WHR]. Fasting venous blood was collected to measure adipocytokines [leptin and adiponectin] and lipid profile [total cholesterol [TC], total triglycerides [TG], high-density hpoprotein cholesterol HDL-C, low-density lip oprotein cholesterol [LDL-C] and the LDL-C/HDL-C ratio was calculated as the atherogenic index. Then the examined subjects were divided into two groups based on their Waist/hip ratio [WHR]. Group 1 [n 25 with WHR>0.8], and group2 [n=15 with WHR