Quercetin ameliorates Di (2-ethylhexyl) phthalate-induced nephrotoxicity by inhibiting NF-κB signaling pathway.

This study aimed to evaluate the possible protective effects of quercetin, a natural flavonoid, against nephrotoxicity induced by Di (2-ethylhexyl) phthalate (DEHP) in kidney tissue of rats and human embryonic kidney (HEK) 293 cell line. The HEK-293 cells were treated with different concentrations of quercetin 24 h before treatment with monoethylhexyl phthalate (MEHP). Male rats were treated with 200-mg/kg DEHP, 200-mg/kg DEHP plus quercetin (50 and 100 mg/kg), and 200-mg/kg DEHP plus vitamin E (20 mg/kg) for 45 days by gavage. Quercetin treatment reduced cytotoxicity and oxidative damage inducing by MEHP in HEK-293 cells. The in vivo findings showed that 100-mg/kg quercetin significantly suppressed DEHP-induced kidney damage. For exploring the involved mechanisms, the expressions of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor kappa B (NFκB), and tumor necrosis factor alpha (TNFα) genes were determined via real-time Polymerase chain reaction (PCR) assay. High dose of quercetin significantly decreased the gene expressions of NF-κB and TNFα, whereas the alternations of Nrf2 and HO-1 gene expressions were not significant in quercetin groups in compared with DEHP group. These findings suggested that the suppression of DEHP-induced nephrotoxicity via quercetin is correlated, at least in part, with its potential to regulate NF-κB signaling pathway.

Phytochemical identification, acute and subchronic oral toxicity assessments of hydroalcoholic extract of Acroptilon repens in BALB/c mice: A toxicological and mechanistic study.

Acroptilon repens (L.) DC, commonly known as Rhaponticum repens, is a popular traditional phytomedicine. The current study was conducted to evaluate the acute and subchronic toxicity of the hydroalcoholic extract of this herb with regard to its terpenoid contents in a BALB/c mice model and to investigate the toxicity of this medicinal herb. Identification of extract components of the plant was done using gas chromatography (GC)-mass spectrometry. In order to establish the acute toxicity model, a single dose of 2000 mg/kg of the extract was given orally to male mice and in the subchronic toxicity study, the extract was consecutively administered at doses 250, 500, and 1000 mg/kg for 28 days. After 28 and 42 days, signs of toxicity and mortality were observed. Organ weight changes and the toxicity-associated parameters such as biochemical indicators, oxidative stress indices, mitochondrial parameters, apoptosis-associated gene expression levels, and pro-inflammatory cytokines were evaluated along with the histopathological examination. GC analysis showed that the terpenoids are the major components of the extract. The LD50 value (2 g/kg) was obtained in the acute toxicity assay; the subchronic administration caused a significant elevation in the serum biomarkers as well as in the levels of lipid peroxidation, protein carbonyl, and ROS. Besides, significant reductions in the superoxide dismutase and catalase activities were observed. This toxic effect was further confirmed by histological studies, cytokine assay, and gene expression assays. Following the treatment discontinuation, the abnormalities in the values of biochemical parameters and histopathological changes returned to normal. These findings demonstrate that the subchronic administration of the hydroalcoholic extract of A. repens can reversibly cause toxicity by inducing oxidative stress and mitochondrial dysfunction.

The Protective Effects of L-Carnitine and Zinc Oxide Nanoparticles Against Diabetic Injury on Sex Steroid Hormones Levels, Oxidative Stress, and Ovarian Histopathological Changes in Rat.

Diabetes mellitus is a common chronic metabolic disorder. This study aimed to investigate the effects of co-treatment with L-carnitine (LC) and zinc oxide nanoparticles (ZnONPs) on serum levels of sex hormones, oxidative stress, and ovarian histopathology in streptozotocin (STZ)-induced diabetic rats. Female Wistar rats (n = 56, 180-220 g) received a single intraperitoneal (IP) injection of STZ (65 mg/kg). They were randomly assigned into the following groups: diabetic group (Dia), Dia+Met group (100 mg metformin/kg/day), Dia+LC group (200 mg/kg/day), Dia+ZnONPs group (10 mg/kg/day), and Dia+LC+ZnONPs group (200 mg LC/kg/day and 10 mg ZnONPs/kg/day). Control group (Ctl) received the same volume of STZ solvent. After 21 days of treatment, blood serum was centrifuged for sex hormone assays. The right ovary was used for biochemical analysis, and the left ovary was fixed in 10% neutral buffered formalin for histological assessment. The levels of estradiol, progesterone, FSH, and LH significantly increased in the Dia+ZnONPs+LC group (P < 0.001) compared with the Dia group. Co-treatment with LC and ZnONPs reduced malondialdehyde and carbonyl protein and increased glutathione, catalase, and superoxide dismutase activities in ovarian tissue compared with the Dia group (P < 0.05). Moreover, the number of all ovarian follicles significantly increased in this group compared with the Dia group (P < 0.05). The results of this study indicated that co-treatment with LC and ZnONPs could preserve ovarian function by increasing sex hormones levels and antioxidant activity and decreasing lipid peroxidation in diabetic rats. Therefore, this compound supplementation may improve ovulation and fertility in people with diabetes mellitus.

Coenzyme Q10 remarkably improves the bio-energetic function of rat liver mitochondria treated with statins.

CoQ10 shares a biosynthetic pathway with cholesterol therefore it can be a potential target of the widely available lipid-lowering agents such as statins. Statins are the most widely prescribed cholesterol-lowering drugs with the ability to inhibit HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase. Preclinical and clinical safety data have shown that statins do not cause serious adverse effects in humans. However, their long-term administration is associated with a variety of myopatic complaints. The aim of this study was to investigate whether CoQ10 supplementation of animals under high fat diet (HFD) treated with statins is able to bypass the mitochondrial metabolic defects or not? Animals were divided into 7 groups and fed with either regular (RD) or HFD during experiments. The first group considered as regular control and fed with a RD. Groups 2-7 including HFD control, CoQ10 (10mg/kg), simvastatin (30mg/kg), atorvastatin (30mg/kg), simvastatin+CoQ10 or atorvastatin+CoQ10 treated orally for 30 days and fed with HFD. At the end of treatments, the animals were killed and blood samples were collected for biochemical examinations. The rat liver mitochondria were isolated and several mitochondrial indices including succinate dehydrogenase activity (SDA), ATP levels, mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPP) were determined. We found that triglyceride (Tg), cholesterol (Chol) and low-density lipoprotein (LDL) were augmented with HFD compared to RD and treatment with statins remarkably lowered the Tg, Chol and LDL levels. Mitochondrial parameters including, SDA, ATP levels, MMP and MPP were reduced with statin treatment and improved by co-administration with CoQ10.