Iranian Journal of Toxicology
Volume:14 Issue: 4, Oct 2020

Paraquat poisoning results in multi-organ failure, primarily pulmonary fibrosis, acute renal failure, and hepatic impairment. The present study was designed to evaluate three treatment regimens, such as N-Acetyl cysteine (NAC), silymarin and hydrocortisone in the prevention of lung fibrosis after ingestion of toxic doses of paraquat in rats. 

Male Sprague-Dawley rats (N=20) were randomly divided into four groups of five each. The drugs and paraquat were given to the rats orally. All rat groups received one oral dose of paraquat (10 mg/kg) once daily for 1 week. The first group received a daily oral dose of silymarin (600 mg/kg) for 2 weeks. The second group received a daily oral dose of NAC (500 mg/kg) for 2 weeks. The third group was given daily oral doses of NAC (500 mg/kg) and hydrocortisone (50 mg/kg) for 2 weeks. The fourth group (controls) received no drugs other than paraquat. The experiment continued for 4 weeks. After the experiment, autopsy was performed on all rats and the lungs were examined histopathologically.

The results of histopathology examinations for peribronchial inflammation in the groups were shown that NAC plus hydrocortisone and silymarin had notable effects in the prevention of lung inflammation. Septal widening in the lungs was also observed in group three less than that in the other groups.

Based on the results, silymarin, NAC and hydrocortisone may be used as a palliative treatment in paraquat poisoning specifically aimed at preventing the acute and chronic lung injuries as the worst complication of the poisoning.

Kidneys exposure to toxins can cause injuries, leading to their functional impairments. Traditionally, plants have been used for the treatment of renal disorders and numerous medicinal plants have been tested for their nephroprotective effects, in such cases as gentamicin (GM) and cisplatin (Cisp)-induced nephrotoxicity. This study assessed the ability of Acalypha wilkesiana’s extract to counteract its toxic effect based on the biochemical, histological and proinflammatory cytokines components in rats. 

Thirty-six male Wistar rats were randomly divided into nine groups (n=4 each) and administered the following treatments: a) normal control (1 mL/kg body weight normal saline from days 1-10); b) nephrotoxin (GM 120 mg/kg, days 2-7; or Cisp 7 mg/kg on day 3); c) standard drug (120 mg/kg Silymarin plus GM or Cisp, days 1-10); and, d) extract groups (100 or 250 mg/kg, days 1-10 plus GM). Blood samples were collected and subjected to hematological and biochemical evaluations while kidney tissue samples were examined for histopathological alterations, pro- and antioxidants, and expression of pro-inflammatory cytokines.

Treatment of the rats pre-exposed to GM or Cisp with the extract decreased the serum creatinine, urea and MDA levels. The GST and GPx levels were also restored in rats. Glomerular atrophy with tubular epithelial necrosis induced by either nephrotoxin was restored to near normal. The expression of COX-2 following the administration of either nephrotoxin was reversed after treatment with the extract.

The A. wilkesiana extract exhibited significant nephroprotective property, which could potentially be regarded as a promising alternative to the management of renal diseases.

Sulfites including Sodium Metabisulfite (SMB) are commonly used as food preservatives and pharmaceutical products. Despite their worldwide use, there is evidence suggesting their toxicity on human organs and tissues. The purpose of this study was to evaluate the effect of SMB with or without Zingiber officinale (ginger) extract on the rat ovary. 

A total of 32 adult, female Wistar rats were divided into four groups of eight each. They consisted of, a) control group, b) ginger group (500 mg/kg/day), c) SMB group (260 mg/kg/day), and d) combined SMB and ginger group at identical doses. After 28 days, the rats were sacrificed and the ovarian tissue Malondialdehyde (MDA), as a marker of lipid peroxidation was measured. The volume and weight of the ovaries and the number of follicles at different stages were counted by stereological methods. 

The SMB treatment caused a significant decrease in the ovarian volume and the number of follicles with simultaneous increase in the number of degenerate follicles (P≤0.001) and MDA level (P≤0.01). Ginger treatment of the rats exposed to SMB significantly increased the number of follicles at various stages and partially reversed the ovarian tissue level of MDA, compared to that in the control group (P≤0.05).

The SMB treatment induced structural changes in the rats’ ovaries and the concomitant treatment with ginger largely reversed the damages caused by SMB.

The safety of the use of medicinal plants is a general challenge among consumers. To improve the use, it is necessary to provide complete profiles of the natural medications for quality control and the therapeutic and toxicity effects. This study was conducted to evaluate the structural and functional toxicity of the methanolic extracts of Salvia rhytidea and Glycine max plants in mice. 

After determining the LD50, NMRI mice with mean weight of 25-30 g were treated intraperitoneally with 100, 200 and 400 mg/kg, and orally with 800 mg/kg of the extracts for 7 consecutive days. After the last treatment, the serum samples were prepared and used for the biochemical assays. The liver and left kidney were removed from the animals and fixed in 10% formalin for histopathological examinations. 

The results indicated that the biochemical parameters of liver and kidneys were not significantly different among the experimental and control groups (P>0.05). Mild degenerative changes in the liver and kidneys were observed at the IP dose of 400 mg/kg and oral dose of 800 mg/kg of both extracts. 

The use of these plants’ extracts did not induce severe toxicity in the short-term; however, caution should be exercised with the long-term use.

Non-ionic surfactant, Tween-80 (TW80) is commonly used for drug delivery due to its effect on the cell membrane permeation. The change in permeability can also increase viral infectivity in cells. This study was undertaken to improve upon Newcastle disease virus (NDV) titer cultivated with embryonic chicken eggs. 

The toxicity of TW80 was investigated against chicken embryos at varying concentrations, and changes in the morphology and weights of the heart, liver, and spleen of 4-day old chicken embryos were analyzed. Also, the effect of non-toxic concentrations of TW80 was examined on the infectivity of NDV. The virus was titrated in the allantoic fluid, using a 50% embryo infectious dose (EID50). 

At high concentrations of TW80, hemorrhage-induced mortality was observed in embryos at the early stages of incubation. The embryos’ viability was not affected at low TW80 concentrations, indicating that its toxicity to the chicken embryos was dose-dependent. The infectivity titer of NDV was increased in the presence of TW80 compared to those inoculated with NDV only. 

The data suggest that TW80 is toxic to chicken embryos at high concentrations, but it enhances cell membrane permeability for NDV particles at low concentrations without affecting the embryos’ viability.

Sodium benzoate, a food preservative, prevents the growth of fungi and bacteria. Numerous studies have reported the protective effects of sodium benzoate on the nervous system. This study investigated the effect of sodium benzoate on cell apoptosis and mitochondrial function in an aluminum cell toxicity model.

After 48 hr of treating PC-12 cells with varying concentrations of sodium benzoate (0.125, 0.25 or 0.5 mg/ml) in the presence of aluminum maltolate (500 μM), the cell viability was assessed by MTT assay. The type of cell death (necrosis or apoptosis) was analyzed by flow cytometry (7-ADD/An V-PE staining). Also, rhodamine 123 was used to measure the Mitochondrial Membrane Potential (MMP). The acetylcholinesterase activity (AChE) was assessed by Ellman’s method.

It was observed that sodium benzoate inhibited aluminum induced cell death within 48hr. Sodium benzoate at a concentration of 0.5 mg/ml significantly reduced the apoptotic cells that had been exposed to aluminum. Exposure of PC-12 cells with sodium benzoate and aluminum, increased the AChE activity, although, no significant changes in mitochondrial membrane potential were observed. 

Sodium benzoate may provide its protective effects through increased AChE activity and inhibiting apoptosis induced by aluminum toxicity. It is likely that the disruption of MMP is neither involved in the induction of apoptosis by aluminum nor in the protective effect of sodium benzoate.

Statins frequently cause myopathy especially in combination with fibrates, and physical activity is considered a trigger for the muscle disorder. Elevated plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH) and aldolase, are the main indicators of the severity of myopathy. Carvedilol is commonly used with lipid-lowering drugs in the management of heart failure, hypertension and dyslipidemia. It is not yet clear whether carvedilol, an alpha and β blocker, and anti-oxidant, may influence the development of myopathy when combined with statins and fibrates in cardiac patients. 

In this animal experiment, a 10 days regimen containing oral atorvastatin and gemfibrozil at doses of 80 and 1000 mg/kg/day, respectively, was used to induce myopathy in rats. The animals were forced to swim in a pool on days 8, 9 and 10 into the study. Carvedilol (2.5 mg/kg/day) was added to atorvastatin and gemfibrozil during the 10-day study period, in addition to the exercise protocol given to the treatment groups only. The mean of swimming tolerance times and the serum levels of CK, LDH and aldolase were measured at the completion of the study. 

Carvedilol did not significantly alter the swimming tolerance time or the plasma levels of CK, LDH and aldolase in the rats receiving ATV, GMF and carvedilol plus the exercise protocol, compared with those that did not receive carvedilol (P>0.05).

Carvedilol may be used in combination with lipid-lowering drug in the management of patients with heart failure and hypertension, pending its safety approval by clinical studies in humans.

A syringe to syringe dispersive liquid phase micro-extraction-floating organic drop was applied and used for the simultaneous extraction and pre-concentration of trace amounts of amphetamine (AMP) and methamphetamine (MAMP) in urine samples. The extracted analytes were determined by high performance liquid chromatography along with diode array detection.

In this study, n-hexane was selected as the extraction solvent without the need to use dispersive solvent. The analytical parameters affecting the micro-extraction efficiency, including pH of sample solution, extraction solvent volume, the cycles of extraction and time of centrifugation were investigated and optimized by screening and optimization experimental design methods. 

Underoptimal conditions, the calibration curve had a linear range of 2-100 μg/L with the determination coefficient of R2=99.8 and R2=99.6 for AMP and MAMP, respectively. The limit of detection was 2 μg/L for AMP and MAMP, and the enrichment factor was 75 and 68 for AMP and MAMP, respectively. 

This method is very simple, rapid and has been successfully used for pre-concentration and measurement of the analytes in urine samples, which is important to forensic studies.