TGF-ß Pathway Inhibition Protects the Diaphragm From Sepsis-Induced Wasting and Weakness in Rat.

Sepsis is a frequent complication in patients in intensive care units (ICU). Diaphragm weakness, one of the most common symptoms observed, can lead to weaning problems during mechanical ventilation. Over the last couple of years, members of the transforming growth factor (TGF) ß family, such as myostatin, activin A, and TGF-ß1, have been reported to strongly trigger the activation of protein breakdown involved in muscle wasting. The aim of this study was to investigate the effect of TGF-ß inhibitor LY364947 on the diaphragm during chronic sepsis.Rats were separated into four groups exposed to different experimental conditions: Control group, Septic group, Septic group with inhibitor from day 0 (LY D0), and Septic group with inhibitor from day 1 (LY D1). Sepsis was induced in rats by cecal ligation and puncture, and carried out for 7 days.Chronic sepsis was responsible for a decrease in body weight, food intake and diaphragm's mass. The inhibitor was able to abolish diaphragm wasting only in the LY D1 group. Similarly, LY364947 had a beneficial effect on the diaphragm contraction only for the LY D1 group. SMAD3 was over-expressed and phosphorylated within rats in the Septic group; however, this effect was reversed by LY364947. Calpain-1 and -2 as well as MAFbx were over-expressed within individuals in the Septic group. Yet, calpain-1 and MAFbx expressions were decreased by LY364947.With this work, we demonstrate for the first time that the inhibition of TGF-ß pathway during chronic sepsis protects the diaphragm from wasting and weakness as early as one day post infection. This could lead to more efficient treatment and care for septic patients in ICU.

Potassium Bromate-induced Changes in the Adult Mouse Cerebellum Are Ameliorated by Vanillin.

OBJECTIVE: The current study aimed to elucidate the effect of vanillin on behavioral changes, oxidative stress, and histopathological changes induced by potassium bromate (KBrO3), an environmental pollutant, in the cerebellum of adult mice. METHODS: The animals were divided into four groups: group 1 served as a control, group 2 received KBrO3, group 3 received KBrO3 and vanillin, and group 4 received only vanillin. We then measured behavioral changes, oxidative stress, and molecular and histological changes in the cerebellum. RESULTS: We observed significant behavioral changes in KBrO3-exposed mice. When investigating redox homeostasis in the cerebellum, we found that mice treated with KBrO3 had increased lipid peroxidation and protein oxidation in the cerebellum. These effects were accompanied by decreased Na+-K+ and Mg2+ ATPase activity and antioxidant enzyme gene expression when compared to the control group. Additionally, there was a significant increase in cytokine gene expression in KBrO3-treated mice. Microscopy revealed that KBrO3 intoxication resulted in numerous degenerative changes in the cerebellum that were substantially ameliorated by vanillin supplementation. Co-administration of vanillin blocked the biochemical and molecular anomalies induced by KBrO3. CONCLUSION: Our results demonstrate that vanillin is a potential therapeutic agent for oxidative stress associated with neurodegenerative diseases.

Cytoprotective Effects of the Red Marine Alga Chondrus canaliculatus Against Maneb-Induced Hematotoxicity and Bone Oxidative Damages in Adult Rats.

The current study aimed at evaluating the ability of a mineral and antioxidant-rich extract from Chondrus canaliculatus to improve maneb (MB)-induced toxicity in adult rat. The animals were divided into four groups: group 1 used as a control group, group 2 received MB, group 3 received MB + C. canaliculatus extract, and group 4 received only the algal extract. MB, a Mn-containing ethylene-bis-dithiocarbamate fungicide, induced oxidative stress damages, mineral perturbations in the plasma, urine, and bone, and genotoxicity in rats. Hematological analysis revealed in the MB-treated group a disruption in the number of red blood cells, platelets, and white blood cells associated with a striking genotoxicity. Interestingly, a significant increase in malondialdehyde and advanced oxidation protein product levels in erythrocytes and bones were found. On the other hand, an impairment of the antioxidant status in both tissues was occurred. Along, our results revealed that MB injection caused a striking drop and disruption in bone's mineral rates, especially calcium and phosphorus. These biochemical results were in accordance with the histological and molecular changes. However, co-treatment with C. canaliculatus extract showed, for the first time, that this alga was effective against MB-induced hematotoxicity, genotoxicity, and oxidative stress in the blood and bone and maintained osteomineral metabolism and bone histo-architecture. Such observations might be explained by the strong in vitro antioxidant and antibacterial activities exhibited by the alga, as well as by its high levels in several minerals: calcium, phosphorus, sodium, potassium, magnesium, iron, and zinc.

Increasing maneb doses induces reactive oxygen species overproduction and nephrotoxicity in adult mice.

BACKGROUND AND PURPOSE: The aim of this study was to elucidate the biochemical, molecular and histopathological aspects of the kidney injuries as well as the hematological perturbations induced after adult mice exposure to increasing doses of maneb (MB). MATERIAL AND METHOD: Adult mice were intraperitoneally treated for seven days with four graded doses of MB, corresponding to 1/8, 1/6, 1/4 and 1/2 of its lethal dose (LD50=1500 mg/kg body weight). RESULTS: Hematological analysis revealed a significant disruption in total white blood cells and platelets and a significant decrease in the plasmatic levels of ferrozine in mice treated with 1/8, 1/6 and 1/4 of MB LD50. However, the ferrozine levels increased significantly in the group treated with 1/2 of MB LD50. Evenly, our results showed a significant increase in the levels of malondialdehyde, lipid hydroperoxides, hydrogen peroxide and advanced oxidation protein products in all treated groups. The activities of catalase and glutathione peroxidase decreased significantly in all MB treated mice. Additionally, all treated groups exhibited strong nephrotoxicity signs, including increases in plasma urea, creatinine and albumin levels and lactate dehydrogenase activity, as well as a significant decrease in uric acid levels. Electrophoresis analysis revealed nucleic acid degradation, testifying the genotoxicity of MB. Moreover, the histopathological observations showed severe renal injuries, which could be related to the above mentioned data. CONCLUSIONS: Our data showed, for the first time, that the MB tested doses led to oxidative stress installation causing renal cell damages and lowering all defense systems capacities.