The Nutraceutical Antihypertensive Action of C-Phycocyanin in Chronic Kidney Disease Is Related to the Prevention of Endothelial Dysfunction.

C-phycocyanin (CPC) is an antihypertensive that is not still wholly pharmacologically described. The aim of this study was to evaluate whether CPC counteracts endothelial dysfunction as an antihypertensive mechanism in rats with 5/6 nephrectomy (NFx) as a chronic kidney disease (CKD) model. Twenty-four male Wistar rats were divided into four groups: sham control, sham-treated with CPC (100 mg/Kg/d), NFx, and NFx treated with CPC. Blood pressure was measured each week, and renal function evaluated at the end of the treatment. Afterward, animals were euthanized, and their thoracic aortas were analyzed for endothelium functional test, oxidative stress, and NO production. 5/6 Nephrectomy caused hypertension increasing lipid peroxidation and ROS production, overexpression of inducible nitric oxide synthase (iNOS), reduction in the first-line antioxidant enzymes activities, and reduced-glutathione (GSH) with a down-expression of eNOS. The vasomotor response reduced endothelium-dependent vasodilation in aorta segments exposed to acetylcholine and sodium nitroprusside. However, the treatment with CPC prevented hypertension by reducing oxidative stress, NO system disturbance, and endothelial dysfunction. The CPC treatment did not prevent CKD-caused disturbance in the antioxidant enzymes activities. Therefore, CPC exhibited an antihypertensive activity while avoiding endothelial dysfunction.

Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T4 injection (20 µg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T4 showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T4 completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole.

Lidocaine affects the redox environment and the antioxidant enzymatic system causing oxidative stress in the hippocampus and amygdala of adult rats.

AIMS: Our objective was to investigate if oxidative stress is involved in the neural damage caused by lidocaine. MAIN METHODS: Male Wistar rats were used. The control group received 0.9% saline ip and the treated group received a single 60 mg/kg lidocaine dose ip. On days 1, 2, 5, and 10 after dosing, ten rats were sacrificed and their brains were quickly removed. The amygdala and hippocampus were dissected. Five samples were used to determine lipid peroxidation, reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG). Another five were used to measure antioxidant activities of glutathione peroxidase (GPX), catalase, Cu-Zn SOD (superoxide dismutase), Mn SOD, and total SOD. KEY FINDINGS: Ten days after injection of lidocaine, lipid peroxidation increases in the hippocampus because the ROS are enhanced from day 5, whereas in the amygdala lipid peroxidation and the ROS were enhanced only on the first day postinjection. Lidocaine causes an increased concentration of GSH and GSSG in the hippocampus from the first day. In the amygdala the GSH and GSSG content were increased at day 10. In the hippocampus the catalase activity was enhanced, whereas the total SOD and Cu-Zn SOD activities were decreased. In the amygdala the lidocaine enhances the activities of catalase and GPX, but no SOD isoenzymes were modified. SIGNIFICANCE: In this research we demonstrated that lidocaine affects the redox environment and promotes increases of the oxidative markers both in the hippocampus and amygdala but in a different pattern.