Nadia A. Aleisa

The protection role of heat shock protein 70 (HSP-70) in the testes of cadmium-exposed rats

Cadmium (Cd) is an environmental carcinogenic pollutant known to inactivate several proteins involved in DNA repair systems while at the same time creating an oxidative stress that can result in additional DNA lesions. The testis and the lung are the target organs for cadmium carcinogenesis. Increased production of oxidants in vivo can cause damage to intracellular macromolecules such as DNA, proteins and lipids, which in turn lead to oxidative injury. So, this investigation aimed to evaluate the protective role of L-Carnitine through up regulation of HSPs against DNA damage induced by cadmium chloride. The current study was carried out on forty adult male rats, each with average weight 220-250g., were divided into 4 equal groups. 1st group was received saline solution (0.5 ml/100 g body weight) and kept as control. 2nd group was received 500mg / kg body weight L-Carnitine intraperitoneally (IP). 3rd group was administered 1.2 mg cadmium chloride IP. 4th group was received both cadmium chloride and L-Carnitine simultaneously. The comet assay parameters showed significantly increased HSP70 and DNA damage in testis cells after 10 and 56 days in the third group. Meanwhile, HSP70 showed significantly decreased levels after 10 days and 56 days in the fourth group after L-Carnitine treatment simultaneously with cadmium chloride. The results of the present study demonstrate a damaging effect of cadmium chloride on DNA of the testis cells (with low stress response). This damaging effect increases the synthesis of HSP70 that upregulated by L-Carnitine treatment and showed ameliorative effect of the cells for recovery.

Impact of heavy metal pollution on the hemogram and serum biochemistry of the libyan jird, Meriones libycus

The stress profiles of the hemogram and serum biochemistry were determined in the context of heavy metal (Cd, Cu, Hg, Ni and Pb) exposure in the wild libyan jird, Meriones libycus, from one of Riyadhs polluted areas versus a reference site. Coupling the pronounced drop in platelets (PLT) (28%) and mean platelet volume (MPV) (17%) with the insignificant responses of other red blood cell indices, suggests bone marrow suppression that is characterized by thrombocytopenia as an initial abnormality. The species-specific stress leukogram for M. libycus is expressed by leukocytosis (66%), monocytosis (40%), lymphocytosis (23%) with eosinopenia (81%) and neutropenia (42%). Hyperglycemia (50%), hyper-low-density-lipoproteinemia (38%), hypocortisolism (85%) and hypotriglyceridemia (55%) depicted serum biochemistry profile. In polluted jirds, the elevated activities of pseudocholinesterase (PChE) and serum marker enzymes (alanine aminotransferase ALT, aspartate aminotransferase AST and creatine kinase CK) strongly suggest functional damage of the liver and/or heart. A potential role of PChE in low-density lipoprotein (LDL) metabolism is implied in the joint rise of both indices and in the recognized relationship between PChE and lipid metabolites. While increased utilization in lipid metabolism and energy synthesis could rationalize the inhibition of the normal patterns of triglycerides and lactate dehydrogenase (LDH), the inhibited activities of LDH could additionally be attributed to its hormetic behavior towards low and high metal concentrations. The overall findings presented here documented the relevance of M. libycus in biomonitoring and predicting the risk imposed on human populations living in polluted areas.

Arginine 16 Glycine Polymorphism in β2-Adrenergic Receptor Gene Is Associated with Obesity, Hyperlipidemia, Hyperleptinemia, and Insulin Resistance in Saudis

Background. Several studies have shown an association between codon 16 polymorphism of the β2AR gene and obesity. Methods. We studied the association between Arg16Gly polymorphism and obesity and its influence on anthropometric parameters, lipids, insulin resistance and leptin in Saudi individuals. The study group included 329 individuals (males: 109 and females: 220). Metabolic parameters, including glucose, lipids, insulin, and leptin were analyzed and anthropometric parameters including waist and hip circumference, waist/hip (W/H) ratio, and body mass index (BMI) were measured and HOMA-IR was calculated. Genotyping was conducted by DNA sequencing of 353 bp fragments, carrying the Arg16Gly polymorphic site. Results and Conclusion. Overweight and obese subjects had a significantly higher frequency of Gly16 (0.375 and 0.38, resp.) compared with normal-weight subjects (0.200). In addition, subjects carrying Gly16 allele regardless of their BMI had greater waist and hip circumference, W/H ratio, plasma lipids, leptin, glucose level, and insulin resistance as judged from the HOMA-IR, compared to those with the wild-type allele. The findings of this study show a significant association between the Arg16Gly polymorphism in β2AR gene and the development of insulin resistance, overweight, and obesity in Saudi populations with an influence on the levels of lipid and leptin.

The Gln27Glu polymorphism in β2-adrenergic receptor gene is linked to hypertriglyceridemia, hyperinsulinemia and hyperleptinemia in Saudis.

Backgroundβ2-adrenoceptor (β2AR) gene polymorphism glutamine 27 glutamic acid (Gln27Glu) and Arg16Gly were reported to have an association with obesity and obesity related disorders in some population. We evaluated Gln27Glu polymorphism in the β2AR gene in obese Saudi populations to investigate the association of β2AR gene with obesity and other related metabolic parameters.DesignWe studied possible association of Gln27Glu in β2AR gene with body mass index (BMI), anthropometric measurements and other metabolic parameters. The β2AR gene polymorphism (Gln27Glu) was identified by sequencing PCR products representing locus of interest. Based on BMI, the subjects were divided into three groups, normal weight, overweight and obese. The genotype and allele frequency were calculated separately for each group.ResultsThe allelic frequency of Glu27 did not differ amongst the three groups, though the Glu27 homozygote (Glu/Glu) were more in obese subjects and had higher concentration of triglyceride, leptin and insulin compared to in the Gln27 heterozygotes and Gln/Gln homozygotes.ConclusionsIn this study we were able to provide evidence on the influence of Gln27Glu genetic variant of β2AR gene on lipid phenotypes, insulin and leptin levels in the Saudi populations.

Evaluation of the Possible Protective Role of Quercetin on Letrozole-induced Testicular Injury in Male Albino Rats

Abstract Background: The purpose of this study was to appraise the possible adverse effects of quercetin against the aromatase inhibitor letrozole-induced developmental toxicity potential in male Wistar rats. Methods: Control male albino rats were received vehicles used for flavonoids and vehicle used for letrozole. The rats in the first experimental group received letrozole at 0.04 mg/kg body weight (bwt) for 3 months. The second experimental group was treated with the flavonoid quercetin by gavage at a dose of 50 mg/kg bwt for 10 consecutive days after letrozole administration. Results: Major treatment-related effects of letrozole included a dose-dependent increase in hormone levels and lipid peroxidation following exposure to 0. 04 mg/kg letrozole; and severe abnormalities with severe cellular deformation and disorganization in both spermatogenic and interstitial cells. The seminiferous tubules of the testes of the animals given quercetin and letrozole exhibited a rather normal appearance and the measured hormone levels were restored to nearly the normal levels. Conclusion: Exposure doses of letrozole that are equal to the daily recommended human dose has toxic effects on the spermatogenic lineage in rats, while simultaneous treatment of quercetin and letrozole could prevent the deleterious effects on testicular tissue caused by letrozole administration.

Oxidative stress and antioxidant response to subacute and subchronic iron overload in Wistar rat

Iron saccharate complex ISC is an iron supplement used to optimize erythropoiesis in cases of iron deficiencies. Because of the lack of major mechanisms of iron excretion, excess iron unbound to protective molecules is believed to be involved in catalyzing the generation of reactive oxygen species and induction of oxidative stress. This study employed ISC for the purpose of inducing iron overload and hence investigating the consequent iron toxicity, lipid peroxidation and antioxidant extent in a murine species. Male Wistar rats were given iron as intraperitoneal injections of ISC in subacute (0.2 mg Fe kg−1 for 2 weeks) and subchronic (0.1 mg Fe kg−1 for 4 weeks) doses. In iron-overloaded rats, enhanced hepatic iron accumulation (P > 0.001) attended by increased serum concentrations of malondialdehyde (MDA) (P > 0.001) and activities of antioxidant enzymes (superoxide dismutase SOD, catalase CAT and glutathione peroxidase GPx) (P > 0.001) was pointed out. The demonstrated antioxidant boost is attributed to a sense of equilibrium prompted by the potential of iron-induced oxidative stress to modify antioxidant defense capacity and to modulate susceptibility to oxidative stress. Rats seemed to constantly suffer from oxidative stress based on the consistent rise in MDA that was not overwhelmed by the elevated antioxidant input. The current findings are of informative value in drawing attention to the health hazards of applying higher doses of the commercially used iron supplement ISC. Data are virtually significant in elucidating the higher magnitude of subchronic than subacute iron overload in initiating oxidative stress and antioxidant defense. Both pathways proceeded in a time-dependent rather than dose-dependent manner.