Dysfunction In Wistar Rats Research Articles

The protective effect of recombinant human erythropoietin against cisplatin-induced renal and hepatic dysfunctions in Wistar rats

I read with interest the recently published article by Rjiba-Touati and colleagues, entitled ‘‘The protective effect of recombinant human erythropoietin against cisplatin-induced renal and hepatic dysfunctions in Wistar rats,’’ in the esteemed journal of Human & Experimental Toxicology. The study has focused to explore the protective effect of recombinant human erythropoietin against cisplatin-induced renal and liver dysfunctions. They suggest that erythropoietin treatment restored body weight, organ weight, and organ ratio as well as serum biochemical parameters changed due to cisplatin exposure. I would like to mention a few points about cisplatininduced nephrotoxicity. Recently, I observed that estrogen abolished protective effect of erythropoietin against cisplatin nephrotoxicity in ovariectomized rats. In another experimental study, my colleagues and I found that L-arginine had protective effect against cisplatin nephrotoxicity in male rats; however, it promoted damage in female subjects. We described a gender-related difference in rat model of cisplatin nephrotoxicity. Since, the role of gender in cisplatin nephrotoxicity is not well known, we recently conducted a study on rat model of cisplatin nephrotoxicity and observed that losartan prevented cisplatin nephrotoxicity in male subjects, but it induced tubular damage in female subjects, which might be related to the rennin angiotensin system receptors in the kidneys. Additionally, we recently reported that vitamin E, vitamin C, or losartan had no ameliorative effects against cisplatin nephrotoxicity in the presence of estrogen in ovariectomized rats, which is in agreement with our previous findings. Kidney protective effect of erythropoietin was also shown in our previous studies. Therefore, it is well found that there is a sex difference in the cisplatin nephrotoxicity in rats. It is well known that some conditions that lead to chronic kidney disease are also sex related. The studies published regarding sex difference in cisplatin-induced nephrotoxicity are rare and needs to explore the mechanisms involved especially for gender differences. In this regard, to better understand the factor of gender difference in cisplatin nephrotoxicity, more experimental or clinical studies are suggested.

Evaluation of radioprotective effect of aloe vera and zinc/copper compounds against salivary dysfunction in irradiated rats.

The aim of this study was to evaluate the radioprotective and reparative effects of compounds based on aloe vera, zinc, and copper against salivary gland dysfunction in Wistar rats. A total of 150 Wistar rats were randomly divided into 12 groups, in which the animals received aloe vera and/or zinc and copper. In eight of these groups the animals were also subjected to irradiation before or after administration of the substances. After 27 days, sialometry tests were performed. Data were analyzed using ANOVA and the Tukey test (P < 0.05). Rats that had been administered aloe vera before or after irradiation showed a significantly higher salivary flow rate than rats that had been simply irradiated. When both substances were administered, a statistically significant difference in the salivary flow rate was observed in comparison with the irradiation alone group seven days after irradiation. The present results suggest that aloe vera exerts positive protective and reparative effects, and can be considered a potential radioprotective substance.

Influence of iron sulfate on adipose tissue endocrine dysfunction in Wistar rats

Aim. To study the adipose tissue endocrine function at adipogenic effect development in Wistar rats on high-fat diet and increased iron intake with drinking water. Methods. Animals on standard and high-fat diets were administered 3 mg/l of iron sulfate with drinking water during 3 months. Levels of circulating proinflammatory cytokines (monocyte chemoattractant protein 1, tumor necrosis factor alpha), leptin, adiponectin, serum glucose and insulin, as well as morphometric parameters and iron content in hair and adipose tissue were evaluated. Results. A significant increase in morphometric parameters, hair iron levels was observed in rats taking iron salts compared to the controls, with highest adipose tissue iron level in rats on high-fat diet. At the same time, serum levels of proinflammatory cytokines (monocyte chemoattractant protein 1, tumor necrosis factor alpha) and leptin was also higher in rats obtaining iron with drinking water compared to controls. Increased serum insulin level together with slightly elevated serum glucose level indicated insulin resistance development in rats on high-fat diet, fed with iron. Conclusion. The research shows that, on the one side, iron intake potentiates the adipogenic effect of high-fat diet, and on the other side, acting as a trigger for endocrine dysfunction formation (so called endocrine disruptor).

The protective effect of recombinant human erythropoietin against cisplatin-induced renal and hepatic dysfunctions in Wistar rats

Cisplatin (Cisp) is one of the most effective chemotherapeutic drugs. However, the dose of Cisp is greatly limited by its toxicity. Recombinant human erythropoietin (rhEPO), a hormone that regulates hematopoiesis, has also been shown to exert tissue-protective effects. The purpose of this study was to explore the protective effect of rhEPO against Cisp-induced renal and liver dysfunctions. Adult male Wistar rats were divided into six groups of six each: control, rhEPO-alone group, Cisp-alone group and rhEPO + Cisp group (pretreatment, cotreatment and posttreatment conditions). Our results showed that Cisp-induced a marked renal and liver failure characterized by a significant decrease in body weight, organ weight and organ ratio and a significant increase in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, G-glutamyl transferase, alkaline phosphatase, bilirubin conjugated and bilirubin total levels in serum. Histological examination showed that Cisp caused kidney alterations. rhEPO treatments restored body weight, organ weight and organ ratio as well as serum biochemical parameters changed due to Cisp exposure.

Liver and Kidney Dysfunction in Wistar Rats Exposed to Municipal Landfill Leachate

<b> </b><b> </b>There is limited information on the toxicity of landfill leachate on somatic tissues and organs of mammals. The hepatotoxic and nephrotoxic effects of leachates from Olusosun and Aba-Eku landfills in Southwestern Nigeria in Wistar albino rats were investigated. Rats orally exposed to 1 – 25 % concentrations of each of the test leachates were examined for clinical signs of toxicity and body weight gain during exposure. Blood, liver and kidney of surviving rats were examined for serum biochemical parameters, organ weight gain and histopathology. Clinical toxicity signs include ungroomed hair, reduced activities, hair loss, laboured breathing, reduced feed and fluid consumption, abscess and muscular disorder. There was concentration dependent sex related significant (p<0.05) decrease in body weight and increase absolute and relative liver and kidney weight gain. The test samples caused increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine but decrease albumin and total proteins. These parameters showed sexual dimorphisms. Histopathological lesions in the liver and kidney include mild to severe multifocal degeneration of the hepatocytes, multiple periportal foci, cellular infiltration, interstitial haemorrhage cortical congestion, degenerative epithelia of renal tubules and necrosis. The concentration of heavy metals and anions in the test samples were above standard permissible limits. These findings show the potentials of landfill leachate to induce liver and kidney dysfunction in rat probably via free radical formation and/or direct chemical disruption of the organs. This may be of health risk in animal and human population expose to chemical substances from waste landfills.

Overexpression of Urinary N-Domain ACE in Chronic Kidney Dysfunction in Wistar Rats

Local activation of the renin–angiotensin system (RAS) has been implicated in the pathogenesis of several renal disorders. In this study we investigated how chronic kidney disease (CKD) modulates RAS components in an experimental model. Male Wistar rats were divided into three groups: sham, nephrectomized, and nephrectomized receiving losartan. Chronic kidney disease animals presented decreased renal N-domain angiotensin-converting enzyme (ACE) activity but overexpression of N-domain ACE in urine. Remnant kidneys presented high angiotensin II levels. Losartan treatment increased urine and tissue ACE activity and tissue levels of angiotensins, mainly angiotensin (1–7), and improved renal and histopathologic parameters. Taken together, the authors’ results indicate that pathophysiological changes due to CKD could lead to an increased expression of somatic and N-domain ACE, mainly the 65 kDa isoform, suggesting that this enzyme could be used as a biological urinary marker in CKD.

Neuroprotective effect of Bacopa monniera on ischemia induced brain injury

Purpose Brain stroke is a leading cause of death without effective treatment. B. monniera, an Indian herbal medicine, exerts antioxidant activity and antistress activity by modulating the antioxidative defence system. We wanted to test if B. monniera could alleviate the ischemia induced brain injury and cognitive dysfunction in Wistar rats. Procedure We studied the effect of B. monniera (120 mg kg − 1 , 160 mg kg − 1 and 240 mg kg − 1 P.O.) on transient intracarotid artery (ICA) occlusion induced ischemia by testing the neurobehavioral and biochemical parameters on treated and control rats. Findings B. monniera attenuated the reduced transfer latency in ischemic rats in a step through test and showed a protective effect on ischemia induced memory impairment in the plus maze task. It also showed a marginal improvement in neurodeficit score and fore limb muscle grip strength. B. monniera reduced the infarct size in the ischemic brain. It also decreased nitrite, nitrate and lipid peroxidation and significantly improved catalase activity. Conclusion These observations suggest the neuroprotective and antioxidant activity of B. monniera on ischemia induced brain injury and pave the way for future investigations.

Unaltered hepatic oxidative phosphorylation and mitochondrial permeability transition in wistar rats treated with nimesulide: Relevance for nimesulide toxicity characterization

Nonsteroidal anti-inflammatory drugs have been associated with hepatotoxicity in susceptible patients. One such example is nimesulide, a preferential cyclooxygenase 2-inhibitor, widely used for the treatment of inflammation and pain. It was suggested that nimesulide could exert its hepatotoxicity by altering hepatic mitochondrial function, which was demonstrated in vitro. The objective of this study was to verify whether liver mitochondria isolated from rats treated with doses of nimesulide well above therapeutic levels possessed decreased calcium tolerance and oxidative phosphorylation, which indicates in vivo nimesulide mitochondrial toxicity. Male and female rats received nimesulide or its vehicle twice daily, for 5 days, and were killed on the seventh day for the isolation of liver mitochondria. Mitochondrial respiration, transmembrane electric potential, and calcium tolerance were characterized in all experimental groups. Nimesulide had no effect on liver mitochondrial function. Indexes of mitochondrial integrity, calcium loading capacity, and oxidative phosphorylation efficiency were unchanged between liver mitochondria from treated and control animals. In the animals tested, no evidence of degraded mitochondrial function due to nimesulide administration could be found. The results corroborate the notion that despite recognized in vitro mitochondrial toxicity, nimesulide does not cause detectable mitochondrial dysfunction in Wistar rats, even when administered in much higher concentrations than those known to have anti-inflammatory effects.

The effect of hydroxyl-containing dithiocarbamates on cisplatin-induced long-term renal dysfunction in Wistar rats

The possibility of a slow, longer term deterioration in renal function following the administration of cisplatin has been little studied in animal models. To obtain data on this we have examined renal function and histopathology at 30 days post i.p. cisplatin (5 mg/kg) treatment in female Wistar rats with and without the administration of hydroxyl-containing dithiocarbamates as a protective measure. In contrast to the studies terminated at shorter times, the degree of protection furnished by the use of dithiocarbamates at longer times post-treatment is less impressive. Results suggest that a containing deterioration in renal function occurs at times greater than 1 week post-treatment when such dithiocarbamates are administered at 1 and 3 h post cisplatin. This was evidenced in both several measures of renal function and in the histopathology of the S3 segment of the proximal tubule.