Aluminium (Al) is used in water purification and is also present in several manufactured foods and medicines. Al is known to induce a broad range of physiological, biochemical and behavioural dysfunctions in laboratory animals and humans. This investigation was carried out to investigate the effects of subchronic exposure to Al (as AlCl3) in rats. Sprague-Dawley rats were randomly separated into two groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with Al (as AlCl3, 5 mg/kg body weight) intraperitonally for 10 weeks. Animals were killed and blood samples were analyzed for blood serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) enzyme activities and creatinine, urea (U) and uric acid (UA) levels for evaluating hepatotoxicity and nephrotoxicity. Blood parameters including red blood cells (RBCs), haemoglobin (Hb) concentration, haematocrit (Ht), platelets (PLTs) and white blood cells (WBCs) were compared between control and experimental group to assess haematoxicity. In order to determine the genotoxicity, the number of micronucleated hepatocytes (MNHEPs) was counted in isolated hepatocytes. In addition, histological alterations in liver and kidney samples were investigated. After exposure with Al, the enzymatic activities of ALP, AST, ALT and LDH, and the levels of U and UA significantly increased. RBC, WBC, PLT, Hb and Ht revealed significant decreases in experimental group compared to the control. AlCl3 caused a significant increase in MNHEPs. Furthermore, severe pathological damages were established in both liver and kidney samples. Subchronic exposure to low doses of Al can produce serious dysfunctions in rat blood, liver and kidney, and exposure to this metal can result in greater damages.

Acute pancreatitis (AP) may cause significant persistent multi-organ dysfunction. Carvacrol (CAR) possesses a variety of biological and pharmacological properties. The aim of the present study was to analyze the hepatic protection of CAR on AP induced by cerulein and to explore the underlying mechanism using in vivo studies. The rats were randomized into groups to receive (1) no therapy; (2) 50 lg/kg cerulein at 1-h intervals by four intraperitoneal injection (i.p.); (3) 50, 100 and 200 mg/kg CAR by one i.p.; and (4) cerulein ? CAR after 2 h of cerulein injection. 12 h later, serum was provided to assess the blood AST, ALT and LDH values. Also, liver tissues were obtained for histological and biochemical measurements. Liver oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as MDA and changes in tissue antioxidant enzyme levels, SOD, CAT and GSHPx. Histopathological examination was performed using scoring systems. Oxidative damage to DNA was quantitated in studied tissues of experimental animals by measuring the increase in 8-hydroxydeoxyguanosine (8-OHdG) formations. We found that the increasing doses of CAR decreased pancreatitisinduced MDA and 8-OH-dG levels. Moreover, the liver SOD, CAT and GSH-Px activities in the AP ? CAR group were higher than that of the rats in the AP group. In the treatment groups, AST, ALT and LDH were reduced. Besides, necrosis, coagulation and inflammation in the liver were alleviated (p \ 0.05). We suggest that CAR could be a safe and potent new drug candidate for treating AP through its antioxidative mechanism of action for the treatment of a wide range of disorders related to hepatic dysfunction.

The most potent of the dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is a persistent and ubiquitous environmental contaminant. And the health impact of exposure to TCDD is of great concern to the general public. Recent data indicate that Lglutamine (Gln) has antioxidant properties and may influence hepatotoxicity. The objective of the present study was undertaken to explore the effectiveness of Gln in alleviating the hepatotoxicity of TCDD on primary cultured rat hepatocytes. Gln (0.5, 1 and 2 mM) was added to cultures alone or simultaneously with TCDD (0.005 and 0.01 mM). The hepatocytes were treated with TCDD and Gln for 48 h. Then cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC), total glutathione (TGSH) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by liver micronucleus assay (MN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT and LDH assays showed that TCDD decreased cell viability but not L-glutamine. TCDD also increased TOS level in rat hepatocytes and significantly decreased TAC and TGSH levels. On the basis of increasing doses, the dioxin in a dosedependent manner caused significant increases of micronucleated hepatocytes (MNHEPs) and 8-OH-dG as compared to control culture. Whereas, in cultures exposured with Gln alone, TOS levels were not changed and TAC and TGSH together were significantly increased in dose-dependent fashion. The presence of Gln with TCDD modulated the hepatotoxic effects of TCDD on primary hepatocytes cultures. Noteworthy, Gln has a protective effect against TCDD-mediated DNA damages. As conclusion, we reported here an increased potential therapeutic significance of L-glutamine in TCDD-mediated hepatic injury for the first time.

Context: The aqueous extracts of Cetraria islandica (L.) Ach. (Parmeliaceae) is traditionally used in many countries against a number of conditions, including inflammatory conditions. Objective: The present study aimed to assess, for the first time, the effectiveness of C. islandica in cultured primary blood cells of Type 1 diabetes subjects. Materials and methods: Diabetic and control blood samples were treated with or without aqueous lichen extract (5 and 10 mg mL À1) for 48 h. The activity of antioxidant enzymes in erythrocytes and also malondialdehyde levels in plasma were determined to evaluate the oxidative status. DNA damages were analyzed by SCE, MN and comet assays in cultured human lymphocytes. Additionally, proliferation index (PI) was evaluated in peripheral blood lymphocytes. Results: There were significant increases in observed total DNA damage (comet assay) (240.2%) and SCE (168.8%), but not in MN frequencies of cultures with diabetes as compared (p40.05) to controls. Whereas, the significant reductions of total DNA damage (69.2 and 65.3%) and SCE frequencies (17.7 and 12.3%) were determined when the 5 and 10 mg mL À1 lichen extract was added to the cell culture medium, respectively. However, lichen extract did not completely inhibit the induction of SCEs in lymphocytes of patients with diabetes. C. islandica extract was also useful on PI rates. Discussion: In conclusion, the antioxidant role of C. islandica in alleviating diabetes-induced genomic instability and for increasing cell viability was firstly indicated in the present study.

Lichens are symbiotic organisms composed of a fungus joined to a photosynthesizing partner that can be either an alga or a cyanobacterium. They can be used as a novel bioresource for natural antioxidants. However, there is also a need for further studies to validate the lichens used in medicinal remedies. This study covers a previously unrecognized effects of Cetraria islandica (CIAE) and Pseudevernia furfuracea (PFAE) in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250-500 mg/kg/day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anesthetized, metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of kidney was examined using four different staining methods: hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), Masson trichrome and Congo red. Our experimental data showed that increasing doses of CIAE and PFAE did not have any detrimental effects on the studied parameters and the malondialdehyde level of kidney. CIAE extract showed prominent results compared to doses of PFAE extract for antioxidant capacity. However, the protective effect of CIAE extract was inadequate on diabetes-induced disorders and kidney damages. Moreover, animals subjected to diabetes mellitus (DM) therapy did not benefit unfortunately from the usage of increasing lichen doses due to their unchanged antioxidant activity to tissue. The results obtained in present study suggested that CIAE and PFAE are safe but the power of these is limited because of the intensive oxidative stress in kidney of type 1 diabetic rats. It is also implied that CIAE extract is especially suitable for different administration routes in DM.

Lichens can be used as a novel bioresource for natural antioxidants. However, there is need for further investigations to validate the lichens used in medicinal remedies. In this study, the effects of Cetraria islandica and Pseudevernia furfuracae lichen species in streptozotocin (STZ)-induced diabetes were evaluated. Diabetic rats were treated with aqueous lichen extracts (250 and 500 mg/kg/day) for 2 weeks starting at 72 h after STZ injection. On the 14th day, animals were anesthetized, and then metabolic and biochemical parameters were evaluated between control and treatment groups. Pancreatic histology and β-cell mass were examined by hematoxylin and eosin and insulin immunohistochemistry stainings. Our findings revealed that these lichen species could be used safely in this dose range. In addition, C. islandica extracts showed prominent results compared to the doses of P. furfuracae extract for antioxidant capacity. However, the protectivity of C. islandica extract was inadequate against diabetes-induced pancreatic damages via forming oxidative stress. In conclusion, the usage of C. islandica might serve for early intervening in the risk reduction of type 1 diabetes.

Oxidative stress plays an important role in causing diabetes; however, no studies have thoroughly reported on the toxic and beneficial effects of lichen extracts in patients with diabetes mellitus (DM). This study covers a previously unrecognized effect of two well-known lichen species Cetraria islandica and Pseudevernia furfuracae in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250-500 mg/kg /day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anaesthetized, and metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of liver was examined using three different staining methods: hematoxylin-eosin (H&E), periodic acid Schiff (PAS), and reticulin and Sudan Black B. Our experimental data showed that increasing doses of C. islandica and P. furfuracae alone did not have any detrimental effects on studied parameters and the malondialdehyde level of liver.C. islandicaextract showed positive results for antioxidant capacity compared to doses of P. furfuracae extract. However, the protective effect of C. islandica extract on diabetes-induced disorders and hepatic damages is still unclear. Moreover, unfortunately, animals subjected to DM therapy did not benefit from the usage of increasing lichen doses due to their unchanged antioxidant activity in tissues. The results obtained in present study suggested that C. islandica and P. furfuracae is safe but the power of these is limited because of intensive oxidative stress in liver of type 1 diabetic rats. It is also implied that C. islandica extract is especially suitable for different administration routes in DM animals.

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