Fibronectin and interleukin-18 renal ischemia with and without reperfusion rats

Ischemia reperfusion is a common leading cause to acute renal failure. Cellular mechanisms include cell adhesion, cell infiltration and generation of oxygen free radicals, and inflammatory cytokine production have been identified, however, the exact causes remain unclear. The aim of the present study was to investigate the role offibronectin [FN], interleukin-18 [IL-18] and serum ferritin in a vivo model of unilateral ischemic and/or reperfused kidney in the rat. In addition, the effects of different durations of ischemia, with or without reperfission on the previous parameters were assessed. This study was carried out on 40 male albino rats divided into 4 groups [10 rats/each]. They were group I: rats were subjected to renal ischemia for 40 minutes without reperfusion; group II: rats were subjected to permanent renal ischemia for 24 hour; group III: rats were subjected to renal ischemia for 40 minutes followed by 24 hour of reperfusion and group IV: sham operated rats. Renal ischemia was induced by clamping the renal artery and vein for 40 or 24 hour mm whereas the contralateral kidney is left intact. At the determined time of sacrifice the blood was collected by cardiac puncture and serum was separated. Both kidneys [left postischemic and right contralateral] were excised and frozen at-80 C for biochemistry. The kidneys were homogenized and used for estimation of fibronectin and IL-18 by EL1SA and serum samples were used to estimate the ferritin by ELISA. The mean value of FN and IL-18 was peaked at 24 h after permanent ischemia in group II, it was significantly high compared with the other studied groups. Forty minutes of ischemia without reperfusion was associated with increased level of FN and IL-18 compared with 40 minutes ischemia with subsequent reperfusion. However, the difference was not statistically significant. Forty minutes ischemia without repeifusion in group I was associated with the highest signicant increase in serum ferritin level. In conclusion, ischemia with or without reperfusion was associated with upregulation of the detected extracellular matrix proteins; spec [flcally FN as well as the detected cytokine; IL-18 from renal tissues. However, the highest increase in these two parameters was observed in permanent ischemia [for 24h] rather than transient ischemia [40 minutes]. The elevated level of FN in permanent ischemia explains its possible role in the regeneration of the damaged kidney and/or fibrosis. Reperfusion has no prominent effect on renal FN and IL-18 levels. Thus, time of ischemia may be the most important determinant for higher FN and 11-18. Moreover, this study had showed that serum ferritin increased significantly in transient ischemia without reperfusion which indicates its role as an acute phase reactant in a response to ischemia

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

Physiologic effects of maternal separation on rat brain neurochemistry: comparative study

Exposure to maternal separation in early life is associated with alteration in the neuroendocrine and neurotransmitter system which may be associated with risk of psychiatric disorders development at adulthood. The aim of this study was to [i] assess levels of monoamines [dopamine, nor-epinephrine, epinephrine and serotonin] in rat pup's brain following repeated maternal separation [RMS] and maternal deprivation [MD]. [ii] Assess brain corticosterone and oxytocin level following both RMS and MD. This study was carried out on 50 male rat pups divided into 3 experimental groups; Group I: 20 rats subjected to 3 h of repeated maternal separation for 14 days; Group II: 20 rats subjected to 24 h of maternal deprivation; Group III: 10 rats served as control group. At the end of the experimental period, all rats were sacrificed and their brains were rapidly removed and dissected for estimation of monoamines, corticosterone and oxytocin. Brain corticosterone level showed marked increase after both separation procedures, however, MD was associated with marked increase. RMS was associated with higher level of epinephrine, norepinephrine, dopamine and serotonin. Dopamine and serotonin levels however, were reduced after MD. Oxytocin level showed marked reduction after MD and RMS. The current work provided some neurobiological evidence supporting the determinant role of mother-infant relationship in the development of psychopathology. Maternal separation leads to profound alterations in the central neurotransmitter system and therefore is associated with increased risk of psychiatric disorders as depression and anxiety. Moreover, maternal separation has impact on the corticosterone and oxytocin release in the brain. Different separation procedures however, can influence the consequences of MS