Subacute exposure to dimethoate induces hepatotoxic and nephrotoxic effects on male rats: Ameliorative effects of ferulic acid

Dimethoate commonly used as environmental ares for control pests which is widely used throughout in the world and itcaused toxic effects on nontarget organisms especially mammalian. Ferulic acid is known to protective compound generally used in toxicology studies. Thus, inthis study, we investigatedthe protective role of ferulic acid against the possible toxic effects of low and high doses of dimethoate. Male rats were randomly divided into six groups: control; ferulic acid; low and high dose dimethoate; both ferulic acid and low dose dimethoate; both ferulic acid and high dose dimethoate. The dimethoate treatment to rats caused oxidative stress in liver and kidney tissue via increased malondialdehyde levels and changes in superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase activities. All dose dimethoate treatments also caused histopathological alterations and differences in activities in alanine aminotransferase, aspartate aminotransferase, total protein, albumin, lactate dehydrogenase, total cholesterol, urea, uric acid, and creatinine levels. The histopathological results verified the biochemical findings for both liver and kidney. Co-administration of ferulic acid with dimethoate improved antioxidative parameters and eased some biochemical parameters mentioned above. Ferulic acid was also seen to play a beneficial role in the histopathological effects of dimethoate for both liver and kidney.

Safety Evaluation of Jiaotaiwan Based on Zebrafish Model / 中国实验方剂学杂志

Objective:To take zebrafish embryo as the research object, in order to investigate the development toxicity, cardiotoxicity, liver toxicity and kidney toxicity of water extract of Jiaotaiwan (JTW) on zebrafish embryo. Method:Zebrafish embryos with normal development at 12 h (hpf) after fertilization were selected as model animals for the growth and cardiotoxicity experiments. The embryos were treated with 125, 250, 500 mg·L-1 of JTW water extracts, and the effects of the drugs on the heart rate and morphology of the embryos and LD50 were observed at 72 h (hpf) after fertilization. Zebrafish embryos with normal development at 72 h (hpf) after fertilization were used as model animals for the liver and kidney toxicity experiments. The embryos were treated with 125，250，500 mg·L-1 of JTW water extracts, and the effect of the drugs on morphological changes, Alanine aminotransferase(ALT), Aspartate aminotransferase (AST) activity, and creatinine content of the larvae and LD50 were observed at 72 d (dpf) after fertilization. Result:The zebrafish embryos in control group developed normally, the heart was well developed, and the heartbeat was even and powerful. The LD50 of JTW water extract on zebrafish embryos for 72 h was 1 023 mg·L-1. Compared with the embryos in the control group, 250，500 mg·L-1 treatment groups in the development toxicity had a smaller head, shorter body lengths (P<0.05), and decreased eye size (P<0.05). Compared with the control group embryos, the pericardial edema was observed in the 500 mg·L-1 group, the heart rate was significantly decreased in the 250，500 mg·L-1 JTW water extract groups (P<0.01), the atrial and ventricular areas were significantly reduced (P<0.05), the distance of SV-BA became significantly larger (P<0.05), the distance of AV channel became significantly larger (P<0.01), and the in-flow distance was significantly shorter (P<0.01). In the acute toxicity experiment, the LD50 of JTW water extract for zebrafish larvae for 72 h was 1 067 mg·L-1. Compared with control group, JTW water extract significantly reduced ALT activity in zebrafish larvae (P<0.05). Conclusion:This experiment found that JTW has an obvious toxicity in embryonic development, which is mainly manifested as delayed growth and severe cardiotoxicity. Great attention shall be paid to clinical administration to pregnant women, lactating women and patients with heart disease.

Safety Evaluation of Over-ground Parts of Glycyrrhiza uralensis / 中国实验方剂学杂志

Objective: To evaluate the toxicological safety of over-ground parts of Glycyrrhiza uralensis, in order to provide basis for the rational utilization of over-ground parts of Glycyrrhizae Radix et Rhizoma recourses.Method: Mice acute oral toxicity test, micronucleus test of mice bone marrow, mice sperm shape abnormality test and toxicological test based on chronic nonbacterial prostatitis model were carried out.Result: Maximal tolerable dose(MTD) of over-ground parts of G.uralensis water extract (WE) and alcohol extract (AE) were 96,128 g·kg-1, respectively. Macro-porous resin enriched product of AE was harmful to mice, with gender differences. Micronucleus rates of each dose(8,16,32 g·kg-1) group and control group for female mouse were 0.28%, 0.34%, 0.26% and 0.22%, respectively. Micronucleus rates of each dose(8,16,32 g·kg-1) group and control group for male mouse were 0.32%, 0.30%, 0.36% and 0.28%, respectively. Sperm shape abnormality rates of each dose group and control group were 3.16%, 3.01%, 2.67% and 3.23%, respectively. Micronucleus rate and sperm shape abnormality rate had no significant increase compared with the negative control. The 30-day repeated intragastric WE and AE had no effect on the general conditions of the model rats. Compared with normal group, AE group showed a significant decrease in heart weight, and significant increases in liver weight, liver index and kidney index (PPConclusion: The results indicated that both of WE and AE have potential toxicity. WE does not show any genetic toxicity to mice. Therefore, further studies shall be made for toxicological safety of over-ground parts of G. uralensis.

Kidney Toxicity Induced by 13 Weeks Exposure to the Fruiting Body of Paecilomyces sinclairii in Rats

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (beta2m), glutathione S-transferase alpha (GST-alpha), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

Three different dividing dosage of DDP combined with chemotherapy to treat moderate and advanced tumors / 中国癌症杂志

Purpose:To ascertain the curative effect and side effects from three different dividing dosage of DDP. Methods:315 cases of moderate and advanced tumors mainly treated with DDP and combined with chemotherapy were divided into 3 groups: (1)DDP 100 ml once(none divided group);(2) 30 to 40 ml of DDP per day, using continuously for 2 to 3 days(middle divided group); (3) 20 ml of DDP per day, using continuously for 5 days(small divided group). And 1 to 3 kinds of other chemotherapy medicines were used at same time. After using the above medicines, the curative effect, main reaction of nausea and vomiting and kidney toxicity were analysed. Results:The curative effect is better in group 1 and 2,but not so good in groups 3. The reaction of nausea and vomiting is slight in the group 2, and the kidney toxicity is high in group 1. Conclusions:The group 2 gets a good curative effect and only slight side effects, and is easy to apply. [