Waterpipe smoke inhalation induces lung injury and aortic endothelial dysfunction in mice.

Waterpipe tobacco smoking (WPS) inhalation has been shown to trigger endothelial dysfunction and atherosclerosis. However, the mechanisms underlying these effects are still unknown. Here, we assessed the impact and underlying mechanism of WPS exposure for one month on endothelial dysfunction using aortic tissue of mice. The duration of the session was 30 min/day and 5 days/week. Control mice were exposed to air. Inhalation of WPS induced an increase in the number of macrophages and neutrophils and the concentrations of protein, tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1beta, and glutathione in bronchoalveolar lavage fluid. Moreover, the concentrations of proinflammatory cytokines (TNF alpha, IL-6 and IL-1beta), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin and P-selectin) and markers of oxidative stress (lipid peroxidation, glutathione, superoxide dismutase and nitric oxide) in aortic homogenates of mice exposed to WPS were significantly augmented compared with air exposed mice. Likewise, the concentration of galectin-3 was significantly increased in the aortic homogenates of mice exposed to WPS compared with control group. WPS inhalation induced vascular DNA damage assessed by comet assay and apoptosis characterized by a significant increase in cleaved caspase-3. While the aortic expression of phosphorylated nuclear factor kappaB (NF-kappaB) was significantly increased following WPS inhalation, the concentration of sirtuin 1 (SIRT1) was significantly decreased in WPS group compared with air-exposed group. In conclusion, our study provided evidence that WPS inhalation triggers lung injury and endothelial inflammation, oxidative stress and apoptosis which were associated with nuclear factor-kappaB activation and SIRT1 down-regulation.

Ellagic acid protects against cisplatin-induced nephrotoxicity in rats: a dose-dependent study.

BACKGROUND: The anticancerdrug cisplatin (CP) causes nephrotoxicity through different mechanisms, including generation of free radicals. Ellagic acid (EA) is a polyphenolic antioxidant found in fruits and nuts. AIM: This study aimed to investigate the ability of different doses of EA to ameliorate CP nephrotoxicity in rats. MATERIALS AND METHODS: Animals were randomly divided into six groups and treated with saline; CP alone (6 mg/kg); two doses of EA, both alone (10 and 30 mg/kg) or with CP. RESULTS: Treatment with CP alone reduced body weight, water intake, urine output, and renal total antioxidant and reduced glutathione (GSH) concentrations (p < 0.01). In addition, it increased relative kidney weight, plasma creatinine, and blood urea nitrogen (BUN) concentrations (p < 0.01). However, a dose of 30 mg/kg EA mitigated most of the CP-induced actions, but no effect was seen for the 10 mg/kg dose. Histopathologically, rats given CP+EA30 showed < 25% necrotic lesions in the renal cortical area compared with > 60% in rats treated with CP alone. Molecular analysis showed that clusterin (Clu) mRNA and protein were expressed in all treated groups, meanwhile kidney injury molecule-1 (Kim-1) mRNA and protein were only expressed in the CP and CP+EA treated rats. CONCLUSIONS: EA (30 mg/kg) ameliorated most of the physiological, histological, and biochemical markers of CP nephrotoxicity. The molecular findings in this work did not completely tally with the conventional method used. The overexpression of the molecular markers may be related to the EA induced repair mechanism.

The effect of curcumin on oxaliplatin and cisplatin neurotoxicity in rats: some behavioral, biochemical, and histopathological studies.

Cisplatin is commonly used against several solid tumors, and oxaliplatin is an effective cytotoxic drug used in colorectal cancer. A major clinical issue affecting 10-40 % of patients treated with cisplatin or oxaliplatin is severe peripheral neuropathy causing sensory, motor, and autonomic dysfunction, with symptoms including cold sensitivity and neuropathic pain. The biochemical basis of the neurotoxicity is uncertain, but is associated with oxidative stress. Curcumin (a natural phenolic yellow pigment) has strong antioxidant, anticancer, and anti-inflammatory actions. Here we report the possible protective effect of curcumin on some cisplatin- and oxaliplatin-induced behavioral, biochemical, and histopathological alterations in rats. Twenty-four hours after the end of treatments some motor and behavioral tests (motor activity, thermal and mechanical nociception, and neuromuscular coordination) were conducted, followed by measuring plasma neurotensin platinum concentration in the sciatic nerve, and studying the histopathology of the sciatic nerve. Oxaliplatin (4 mg/kg) and cisplatin (2 mg/kg) [each given twice weekly, in a total of nine intraperitoneal injections over 4.5 weeks] significantly increased plasma neurotensin concentration, caused specific damage in the histology of the sciatic nerve and produced variable effects in the motor and behavioral tests. Oral curcumin (10 mg/kg, 4 days before the platinum drug, and thereafter, concomitantly with it for 4.5 weeks) reversed the alterations in the plasma neurotensin and sciatic nerve platinum concentrations, and markedly improved sciatic nerve histology in the platinum-treated rats. Larger experiments using a wider dose range of oxaliplatin, cisplatin, and curcumin are required to fully elucidate the possible protective role of curcumin in platinum-induced neurotoxicity.

Comparative efficacy of three brands of gum acacia on adenine-induced chronic renal failure in rats.

Gum acacia (GA) is used in pharmaceutical, cosmetic and food industries as an emulsifier and stabilizer, and in some countries in the traditional treatment of patients with chronic kidney disease (CKD). We have previously found that GA ameliorates adenine-induced chronic renal failure (CRF) in rats. Different brands of GA are commercially available, but their comparative efficacy against adenine-induced CKD is unknown. Here, we explored the effects of three different brands of GA (Sudanese GA, Supergum and GA from BDH) on some physiological, biochemical, and histological effects of adenine-induced CRF in rats. Adenine (0.75 %, w/w in feed, four weeks) reduced body weight, and increased urine output. It also induced significant increases in blood pressure, and in creatinine, urea, several inflammatory cytokines in plasma, and indices of oxidative stress, and caused histological damage in kidneys. Treatment of rats concomitantly with any of the three GA brands, significantly, and to a broadly similar extent, mitigated all the signs of CRF. The results suggested equivalent efficacy of these brands in antagonizing the CRF in this animal model. However, to enable standardization of different brands between laboratories, the use of the chemically well-characterized GA preparation (such as Supergum) is recommended.