Possible ameliorative effects of hydromethanol extract of Thymus vulgaris on cadmium induced hepatorenal toxicity in rats

This study evaluated the possible ameliorative effect of hydromethanol extract of Thymus vulgaris on hepatorenal toxicity induced by cadmium in male rats. The experimental animals were divided into four groups and treated as follows: A (control - 0.5ml of 2% tween 80 in distilled water per os) for 3 weeks and a single subcutaneous dose of phosphate buffered saline, B (single subcutaneous dose of cadmium in phosphate buffered saline at 3 mg/kg); C (500 mg/kg extract per os daily for 3 weeks) and D (single subcutaneous dose of cadmium in phosphate buffered saline at 3 mg/kg + 500 mg/kg extract per os daily for 3 weeks). Cadmium administration resulted in suppression of erythrocyte count, hemoglobin concentration, packed cell volume, an elevated total leucocyte count with associated neutrophilia which improved with extract administration. Levels of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, creatinine and total bilirubin concentration increased with decrease in total serum protein and albumin in cadmium treated group B compared to control group A, group C (extract only) and cadmium plus extract treated group D. Cadmium led to a reduction in catalase and superoxide dismutase activities with increase in the level of malondialdehyde. However, co-administration of extract with cadmium in group D reduced lipid peroxidation and oxidative stress induced by cadmium. Histopathological examination of cadmium treated groups showed moderate vacuolar degeneration in the liver and degeneration of the kidney tubules which were ameliorated following co-administration with extract. This study shows that Thymus vulgaris extract has a potential protective effect against cadmium induced hepato-renal injury through the suppression of oxidative stress.

Activation of Innate Immunity in Healthy Macaca mulatta Macaques by a Single Subcutaneous Dose of GMP CpG 7909: Safety Data and Interferon-Inducible Protein-10 Kinetics for Humans and Macaques

ABSTRACT Following a demonstration that mouse-optimized cytosine-guanosine dinucleotide (CpG) oligodeoxynucleotides stimulated innate immune protection against intracellular pathogens, we tested the ability of CpG 7909, a primate-optimized Toll-like receptor 9 (TLR9) agonist, to stimulate rhesus macaques to produce interferon-inducible protein-10 (IP-10), a biomarker of immune activation. This study was performed prior to a similar trial with humans in order to facilitate the development of CpG 7909 as an immunomodulator for biodefense. A single subcutaneous dose of clinical-grade CpG 7909 was given to four groups of healthy adult rhesus macaques (0-mg dose [n = 5], 0.75-mg dose [n = 9], 1.5-mg dose [n = 9], and 3.0-mg dose [n = 9]). Directed physical examination findings, clinical laboratory values, and serum IP-10 concentrations were collected at scheduled intervals for 28 days. All three dose levels of CpG 7909 were safe and not associated with significant clinical or laboratory abnormality. The time to peak serum IP-10 concentration was 1.0 days at the 0.75-mg dose and 0.5 days at the 1.5- and 3.0-mg doses. A dose-dependent response was observed for the magnitude and duration of IP-10 concentrations, which remained significantly above baseline for 3 days for the 3.0-mg and 1.5-mg dose groups but above baseline for only 2 days for the 0.75-mg dose group. There were no nonresponders to CpG 7909. These rhesus macaque safety and IP-10 response data closely parallel a subsequent phase 1 human study of subcutaneously administered CpG 7909. A single dose of clinical-grade CpG 7909 induced a rapid, sustained IP-10 response, a biomarker for activation of the innate immune system. Given the similar susceptibilities of humans and rhesus macaques to infectious diseases, the rhesus macaque appears to be a suitable model to evaluate the potential of CpG 7909-mediated innate immune activation to protect humans against pathogens.