Pathophysiology

Editorial Board

2011-09-01

Antihyperglycemic and antioxidant activities of alcoholic extract of Commiphora mukul gum resin in streptozotocin induced diabetic rats

2011-09-01

Abstract: Background and objectives: The present study investigated the effect of Commiphora mukul ethanol extract gum resin (CMEEt) on streptozotocin (STZ) induced diabetic rats by measuring fasting blood glucose, plasma insulin, plasma lipid profile, atherogenic index, hepatic lipid peroxidation (LPO), protein oxidation (PO) and activities of enzymatic antioxidants. Methods: Wistar albino rats were divided into 4 groups, normal control group, CM-treated control group, diabetic control group and CM-treated diabetic group. For induction of diabetes, STZ was administered at a dose of 55mg/kg body weight, meanwhile CM-treated groups were administered CMEEt at a dose of 200mg/kg body weight for 60 days. Body weight, plasma glucose and insulin levels were determined in different experimental days, after end of the experimental period the plasma lipid profile and antioxidant enzymes were determined in hepatic tissue. Results: Increase in plasma glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), hepatic LPO and PO levels with decrease in plasma high density lipoprotein cholesterol (HDL-C), insulin, hepatic reduced glutathione (GSH) content and activities of antioxidant enzymes namely, glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were the salient features observed in diabetic rats. On the other hand, oral administration of CMEEt at a dose of 200mg/kg for 60 days resulted in the prevention of above mentioned abnormalities. Conclusion: The results suggest that CMEEt could be beneficial in the treatment of diabetes, characterized by atherogenous lipoprotein profile, aggravated antioxidant status and impaired glucose metabolism and in their prevention.

Alteration of rat hippocampal neurogenesis and neuronal nitric oxide synthase expression upon prenatal exposure to tamoxifen

2011-09-01

Abstract: The present study delineates the effect of tamoxifen on neuronal density and expression of neuronal nitric oxide synthase (nNOS) in hippocampal nerve cells during prenatal and postnatal periods in rats. Pregnant rats were administered with tamoxifen one day prior to labor (E21) and on the childbirth day (E22). Hippocampi of embryos at E22 and newborns at postnatal days of 1, 7, and 21 (P1, P7, and P21) were investigated. Density of the neurons in areas of the developing hippocampus including cornu ammonis (CA1, CA3), dentate gyrus, and subiculum were studied. Our findings show that the number of pyramidal neurons was significantly decreased in CA1 and subiculum of tamoxifen-treated rats in E22, P1, and P7. We found that cellular density was lower in early stages of development, however, cellular density and thickness gradually increased during the development particularly in the third week. We found that nNOS expression was decreased in E22, P1, and P7 in animals treated with tamoxifen. The present study shows that tamoxifen affects development and differentiation of postnatal rat hippocampus, CA1 neurons, and nNOS expression.

Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats

2011-09-01

Abstract: Background and objective: Considering the high incidence of cardiovascular disorders in diabetes mellitus and some evidence on the antioxidant and antidiabetic potential of cyanidin-3-glucoside (C3G), this study was conducted to evaluate the possible beneficial effect of C3G administration on vascular reactivity of isolated thoracic aorta in diabetic rats and some of its underlying mechanisms. Materials and methods: Male diabetic rats received C3G (10mg/kg; i.p.) on alternate days for 8 weeks one week after streptozotocin (STZ) diabetes induction. Results: It was found out that treatment of diabetic rats with C3G exerted a hypoglycaemic effect and attenuated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in aortic tissue. Maximum contractile response of endothelium-intact aortic rings to phenylephrine (PE) was significantly lower in C3G-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine (ACh) was significantly higher in C3G-treated diabetic rats as compared to diabetic group. Conclusion: Chronic treatment with C3G may prevent some diabetes-related changes in vascular reactivity observed in diabetic rats directly and/or indirectly due to its hypoglycaemic effect and attenuation of lipid peroxidation and through endothelial-derived factors.

d-Amphetamine-induced cytotoxicity and oxidative stress in isolated rat hepatocytes

Osama S. El-Tawil, Ali H. Abou-Hadeed, Mohamed F. EL-Bab, Abeir A. Shalaby — 2011-09-01

Abstract: Amphetamines (AMP) are potent psychostimulants and commonly used drugs of abuse. Its chronic administration creates tolerance and addiction and also associated with neurotoxicity and hepatocellular damage through oxidative stress. The present study was designed to evaluate the cytotoxic effects as well as the oxidative stress induced by d-amphetamines in isolated rat hepatocytes. Hepatocytes were isolated by collagenase perfusion technique and were exposed to different concentrations of AMP (0.2, 0.4, 0.8 and 1.6mM) in a time-course experiment for up to 2h. AMP exposure induced a significant decrease in cell viability and a significant increase in the leakage of hepatic enzymes {lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and asparate aminotransferase (AST)} in a concentration and time-related manner. In the same experiment, GSH content and thiobarbituric acid reactive substances (TBARS) generation were determined as indices of oxidative stress and lipid peroxidation respectively. AMP exposure results in a significant decrease in cellular GSH content as well as a significant enhancement of TBARS accumulation in a concentration and time-related manners. The obtained results suggested that 2-h exposure of hepatocytes to AMP (0.8mM) was accompanied by submaximal responses. Therefore, a subsequent dose–response experiment was designed to evaluate the role of GSH modulation and oxidative stress in AMP toxicity in hepatocytes at 2h. LDH release and TBARS generation were used as indicators in this experiment. Pretreatment with the GSH-depleting agents, chlorodinitrobenzene (CDNB), buthionine sulfoximine (BSO), or bis(chloroethyl)-nitrosurea (BCNU) enhanced the cytotoxicity of AMP. Conversely, pretreatment with GSH or sulfhydryl compounds such as methionine (MT), cysteine (CYS) or dithiothreitol (DTT) attenuated AMP toxicity. Similarly, co-incubation with enzymatic antioxidants, superoxide dismutase (SOD) or catalase (CAT) or iron chelator, desferroxiamine (DFO) or the hydroxyl radical scavengers, dimethylsulfoxide (DMSO) exhibited significant protection against AMP cytotoxicity. The present results indicate that AMP has a potential cytotoxic effect in isolated rat hepatocytes. AMP cytotoxicity is concentration-dependent. GSH depletion and oxidative stress play an important role in enhancing hepatotoxic potential of AMP in isolated rat hepatocyte. Thiol group-donors, antioxidants, free radical scavengers and iron chelators can play a critical role against AMP-induced cellular damage.

Efficacy of fish liver oil and propolis as neuroprotective agents in pilocarpine epileptic rats treated with valproate

Fathia Mannaa, Karima A. El-Shamy, Kamal A. El-Shaikh, Mahitab El-Kassaby — 2011-09-01

Abstract: Objective: To evaluate the action of fish liver oil and propolis in pilocarpine epileptic rats treated with the anticonvulsant drug valproate. Methods: Seven groups of rats were treated daily for six months: control; fish liver oil (0.4ml/kg b.w); propolis (50mg/kg b.w); pilocarpine-treated rats (epileptic control); epileptic rats treated with valproate (400mg/kg b.w); groups 6 and 7, epileptic rats treated with valproate plus fish liver oil or propolis. Results: Pilocarpine administration caused a significant increase in hippocampal dopamine and serotonin levels accompanied with a significant decrease in their levels in serum. Lipid peroxidation level and LDH activity in hippocampus were significantly increased after pilocarpine treatment whereas Na+/K+-ATPase activity and total antioxidant capacity were significantly decreased compared to the controls. Animals treated with the combined treatments showed a significant improvement in tested parameters towards the normal values of the control. Conclusion: Fish liver oil and propolis when given in combination with valproate, neuroprotected against the neurophysiological disorders induced by pilocarpine epilepsy in rats.

Cajanus indicus leaf protein: Beneficial role in experimental organ pathophysiology. A review

Kasturi Sarkar, Parames C. Sil — 2011-09-01

Abstract: The herb, Cajanus indicus L, has been and is popular for its medicinal value in India and other countries for long. The herb is mainly cultivated for the seeds which are used as pulses and are rich in proteins. People of rural India and some neighboring countries use the aqueous extract of the leaves of the herb against poor liver function and recently it has been found that the extract is not only useful against liver damage but also beneficial for renal failure and a number of other pathophysiological conditions. Intraperitoneal administration of the aqueous protein fraction of the leaves has shown hepatoprotective activity in mice. The protein fraction revealed the presence of a 43kDa protein having antioxidant and other protective properties in organ pathophysiology. The purified protein, CI-protein, scavenges free radicals generated by different free radical inducers and helps providing cytoprotection. Amino acid sequence of CI-protein has some structural similarity with plastocyanin, an electron carrier protein in photosynthesis. The protein has also been found to be active against a number of organ dysfunction inducer chemicals and drugs, like carbon tetrachloride, thioacetamide and acetaminophen. Signal transduction studies suggest that CI-protein exerts its protective action by free radical scavenging and antioxidative properties; it activates NF-κB and Akt without any involvement of ERK1/ERK2 and STAT-3 in acetaminophen induced hepatic pathophysiology. Besides, it reduces both drug and toxin induced cytotoxicity by decreasing the formation and/or scavenging of free radicals involving cytochrome P450, taking part in detoxification of xenobiotics.

Relationship among circulating leukocytes, platelets, and microvascular responses during induction of chronic colitis

2011-09-01

Abstract: The mechanisms by which microvascular alterations contribute to the pathogenesis of the inflammatory bowel diseases (IBDs; Crohn's disease, ulcerative colitis) have not been clearly delineated. The purpose of the current study was to characterize the inflammatory events, microvascular alterations, and blood cell changes that occur in a mouse model of IBD. In this model, CD4+ T-lymphocytes obtained from interleukin-10-deficient mice were injected intraperitoneally into lymphopenic, recombinase-activating gene-1 deficient (RAG−/−) mice. Two groups of control mice were also included: RAG−/− mice and C57BL/6 mice that were injected with phosphate-buffered saline but did not receive the T-cells. Four weeks later, the RAG−/− mice that had received the T-cell transfer showed significant signs of colonic inflammation, but without significant decreases in either body weight or mean arterial blood pressure. T-cell transfer increased the volume % of circulating platelets, while decreasing the number of circulating red blood cells. Additionally, the T-cell transfer tended to increase the circulating numbers of both lymphocytes and neutrophils when compared to unmanipulated RAG−/− mice. First-order colonic arterioles and venules tended to dilate in the colitic mice; however, the dilation was considerably more substantial with higher numbers of circulating leukocytes. The possibility that circulating inflammatory cells initiate the microvascular alterations in colitis warrants further investigation.

Increasing rates of head melanoma in Nordic countries

Örjan Hallberg, Olle Johansson — 2011-09-01

Prior to 1955, melanoma was not a major health problem in Sweden. Since then, the incidence of melanoma occurring on the sun exposed head region has increased approximately 2-fold while the incidence of melanoma on non sun exposed skin has increased by almost 20-fold . Our previous studies highlighted immune disturbing body-resonant radio waves as having a potential etiologic role in the increased incidence of melanoma . Since that time all people who today are younger than 60 have been living in this new environment for all their lives and are now expected to show stable incidents for each age cohort, which also turns out to be the case .

BMSC and CoQ10 improve behavioural recovery and histological outcome in rat model of Parkinson's disease

2011-09-01

Abstract: Objective: This study assessed the ability of a combination treatment of bone marrow stromal cell (BMSC) graft and oral coenzyme (CoQ10) in a rat model of Parkinson's disease (PD) as an appropriate substitute for current Parkinson treatments. The combination treatment was compared to sole treatments of BMSC and CoQ10. Materials and methods: In this experimental study, there were six groups of male Wistar rats: control, sham, lesion, CoQ10, graft BMSC and graft BMSC plus CoQ10. Oral administration of CoQ10 began 1 week before the PD and continued during the entire treatment period. To simulate PD, we injected 6 hydroxydopamine (6OHDA) in rats. BMSC were labelled by 5-bromo-2′-deoxyuridine (Brdu) before transplantation. We assessed behaviour before PD, 2 weeks after PD and 8 weeks after cell transplantation. At the end of the second month of treatment, immunohistochemistry, histology and molecular studies were performed. Results: Behavioural assessment of the CoQ10 group and BMSC group indicated equal recovery in comparison with the lesion group (P<0.01), while the combined treatment of BMSC and CoQ10 showed considerably better recovery compared with the lesion group (P<0.001). There were no signs of gliosis and graft rejection. Immunohistochemistry analysis of Brdu indicated that cells were alive after 2 months of application in host tissue. Cell counts showed significantly greater numbers of neural cells in the combination treatment of BMSC and CoQ10 compared to the other groups. Tyrosine hydroxylase (TH) gene expression levels in the combined therapy group was significantly more than the other experimental groups (P<0.001). Conclusion: The combined use of two neuroprotective treatments and cell replacement therapy can be effective in the treatment of PD, at least in experimental settings.

Case-control study on the use of mobile and cordless phones and the risk for malignant melanoma in the head and neck region

Lennart Hardell, Michael Carlberg, Kjell Hansson Mild, Mikael Eriksson — 2011-09-01

Highlights: ► A case-control study on the use of mobile and cordless phones and the risk for melanoma in the head and neck region. ► A doubled risk was found in the >1–5-year latency group in the most exposed area. ► Highest odds ratio was calculated for first use before the age of 20 years. ► The findings indicate a late carcinogenic effect in melanoma genesis.Abstract: The incidence of cutaneous malignant melanoma has increased during the last decades in Sweden as in many other countries. Besides of ultraviolet radiation and constitutional factors such as light-sensitive skin and poor ability to tan few risk factors are established. Some studies indicate that electromagnetic fields might be of concern. In this case-control study we assessed use of mobile and cordless phones in 347 cases with melanoma in the head and neck region and 1184 controls. These subjects constituted 82% and 80%, respectively, that answered the questionnaire. Overall no increased risk was found. However, in the most exposed area; temporal, cheek and ear, cumulative use >365h of mobile phone yielded in the >1–5-year latency group odds ratio (OR)=2.1, 95% confidence interval (CI)=0.7–6.1 and cordless phone use gave OR=2.1, 95% CI=1.1–3.8. Highest OR was calculated for first use of mobile or cordless phone before the age of 20 years regardless of anatomical localisation in the head and neck region. No interaction was found with established risk factors such as red, medium blond or fair hair colour, blue eyes, skin type I or II (never or sometimes tanned), severe sunburns as teenager or heredity. The results must be interpreted with caution due to low numbers and potential methodological shortcomings in a case-control study. However, the findings might be consistent with a late carcinogenic effect from microwaves, i.e. tumour promotion, but need to be confirmed.

Corrigendum to “Glatiramer acetate recovers microscopic tissue damage in patients with multiple sclerosis: A case–control diffusion imaging study” [Pathophysiology 18 (2011) 61–68]

2011-09-01

In the above mentioned published article, one of the listed co-authors (Diane L. Cookfair) was inadvertently included in the authorship list.