The effect of lithium tetraborate as a novel cardioprotective agent after renal ischemia-reperfusion injury

Abstract Epidemiological studies suggest that acute kidney injury has certain effect on myocardial function. In this study, for the first time, we tested a boron compound namely lithium tetraborate an act as an anti-oxidant and anti-inflammatory agent in ischemia-reperfusion injury. For this, we employed an in vivo rat model with kidney ischemia reperfusion injury to evaluate cardiac injury to clarify the mechanisms of lithium tetraborate. The evaluation of cardiac injury through kidney artery occlusion and reperfusion rat model indicated that lithium tetraborate could (1) reduce oxidative stress-induced endothelial dysfunction; (2) attenuate the inflammatory response of cardiac cells; and (3) alleviate the apoptosis and necrosis of myocytes. In summary, lithium tetraborate demonstrates significant therapeutic properties that contribute to the amelioration of cardiac damage, and it could be a promising candidate for future applications in myocardial dysfunction.

Inula graveolens induces selective cytotoxicity in glioblastoma and chronic leukemia cells.

OBJECTIVE: Crude oil extracts, components of extracts, and ethanolic extracts of Inula graveolens possess various pharmacological activities on various cancer cells including antioxidative and antiproliferative effects. Aqueous extract of this species has not been investigated on the liquid malignancies and solid tumors with a high incidence of treatment refractoriness and poor survival outcomes such as glioblastoma and leukemia. Hence, the present study aimed to evaluate the cytotoxic efficiency of I. graveolens aqueous extracts on human glioblastoma multiforme and chronic myelogenous leukemia cell lines in comparison to non-cancerous primary rat cerebral cortex and human peripheral blood mononuclear cells. METHODS: The cells were treated with the extracts of I. graveolens (125-1000 µg/mL) for 48 h, the cellular viability was identified using 3'-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and lactate dehydrogenase release was measured to determine the cytotoxic potential. Total oxidant status and apurinic/apyrimidinic endodeoxyribonuclease 1 assays were used to determine the oxidative status of cells and DNA damage, respectively. RESULTS: I. graveolens showed selective cytotoxicity toward human glioblastoma multiforme and chronic myelogenous leukemia cell lines and exhibited a higher antiproliferative effect against cancer cells in comparison to non-cancerous cells. Moreover, it significantly reduced the apurinic/apyrimidinic endodeoxyribonuclease 1 levels on both cancer cell lines as compared with their control cells without changing the levels of an oxidative stress marker. CONCLUSION: The extracts of I. graveolens have anti-cancer potential on human glioblastoma multiforme and chronic myelogenous leukemia cell lines without causing oxidative stress.

Antioxidant and anti-apoptotic effects of vitexilactone on cisplatin-induced nephrotoxicity in rats.

Cisplatin (CP) is an antineoplastic drug; however, owing to its nephrotoxicity, its clinical use is limited. We investigated whether vitexilactone (vitex) is a safe and effective treatment for CP induced kidney injury. We allocated Sprague-Dawley rats into six groups: control group, low dose-high dose vitex groups (40 and 80 mg/kg vitex for 6 days before administration of CP), CP group (single 6 mg/kg dose on day 6) and CP + low dose vitex-CP + high dose vitex group (40 and 80 mg/kg vitex for 6 days, and a single 6 mg/kg dose of CP on day 6. Rats were euthanized 5 days after CP treatment. After exposure to CP and/or vitex, total oxidative stress and total antioxidant status were assessed. The histology of the kidney was examined using hematoxylin and eosin, and periodic acid-Schiff. We used immunohistochemical and fluorescence staining to detect expression of caspase-3. We also measured blood urea nitrogen, uric acid and creatinine levels. Nephroprotective effects of vitex were associated with decreased serum toxicity markers and increased antioxidant activity. Vitex also reduced the expression of the apoptosis marker, caspase-3. Treatment with CP increased blood urea nitrogen, uric acid, creatinine levels and total antioxidant status, and decreased total antioxidant status compared to the control group. Use of vitex for protection from CP induced nephrotoxicity appears to be a safe and efficacious alternative for treatment of kidney injury.

The biochemical and histological effects of lichens in normal and diabetic rats.

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.

Effects of lichen extracts on haematological parameters of rats with experimental insulin-dependent diabetes mellitus.

The prevalence of diabetes mellitus in the world is steadily increasing. Oxidative stress contributes to the development of diabetic complications, including diabetic haematological changes. Lichens are used as food supplements and are also used as possible natural antioxidant, antimicrobial and anticancer agents. We hypothesized that antioxidant activity of lichens may decrease hyperglycaemia-induced oxidative stress and prevent the development of diabetic complications, including abnormality in haematological condition. Therefore, the effects of Cetraria islandica water extract (CIWE) and Pseudevernia furfuracea water extract (PFWE) on the haematological parameters of rats with type 1 DM were investigated for the first time in the present study. Control Sprague-Dawley or streptozotocin (STZ)-induced diabetic rats were either untreated or treated with water lichen extracts (5-500 mg/kg body weight (bw)/day) for 2 weeks, starting at 72 h after STZ injection. On day 14, animals were anaesthetized and haematological and metabolic parameters were determined between control and experimental groups. In addition, the total oxidative stress (TOS), a specific indicator of oxidative stress, and the total antioxidant capacity (TAC) were measured by biochemical studies. In diabetic rats, CIWE of 250-500 mg/kg bw dose showed more prominent results when compared with doses of PFWE for TAC. The results obtained in the present study suggested that the antioxidant activities of lichens might be the possible reason behind the observed antihaematological status. However, the protective effect of lichen extracts were inadequate on diabetes-induced microcytic hypochromic anaemia. In addition, the extracts have no effect on metabolic complications. Our experimental data showed that high doses of CIWE and PFWE alone have no detrimental effect on blood cells and TOS status of plasma. Hence, they are safe and suitable for different administration routes.