Iranian Journal of Toxicology
Volume:16 Issue: 2, May 2022

Poisoning due to the bites and stings of venomous snakes and scorpions is a neglected public health problem, particularly in rural areas. Poor health facilities and inadequate knowledge of health care personnel are the major factors that result in envenomated human victims not receiving adequate care and medical attention. There is a great need for up-to-date and effective healthcare knowledge and awareness of the potency and lethality of venomous creatures in Iran. Assessment of the potency, acute toxicity, and lethal effects of venomous creatures come from a variety of specific tests, such as the 50% median lethal dose (LD50) and ample animal experimentations. 

In the present study, using modified Reed-Muench method, the LD0, LD50, and LD100 values of the venoms from five Iranian vipers and one scorpion were determined. The studied venomous creatures were: Macrovipera lebetina, Vipera albicornuta, Vipera raddei, Caucasicus intemedius agkistrodon, Montivipera latifii, and one scorpion Hemiscorpius lepturus. The venoms were injected in Albino mice (n=204) intraperitoneally, and their toxicities determined.

The results revealed that the LD50 values of the above-mentioned creatures were 3.87, 2.05, 1.63, 1.45, 0.84, and 6.33 mg/kg, respectively. Among the vipers, M. latifii had the most potent venom while M. lebetina’s venom had the lowest toxicity.

Theoretically, the determined LD50 values provide for objective comparisons of the toxicity among of the venoms. However, comparison becomes complicated due to variations in the venoms’ LD50. Further, based on the venoms’ toxicity levels, H. lepturus’ venom caused the lowest toxicity in the Albino mice.

Testicular dysfunction is one of the common side effects that results from the treatment with oxaliplatin® as a chemotherapy drug, and pharmaceutical search for agents to relieve the side effects are underway. The current study explored the possible ameliorative and regenerative effects of Costus ethanolic extract against testicular degeneration in male rats induced by oxaliplatin. 

Male Wistar albino rats weighing 150-200g were divided into four groups of 10 rats each as follows: group-1 control rats; group-2 rats treated orally with the extract at 50 mg/kg/day for six weeks; group-3 rats injected oxaliplatin intraperitoneally at 10 mg/kg/week for six successive weeks; group-4 rats were injected intraperitoneally with oxaliplatin at 10 mg/kg/week combined with a daily oral dose of the Costus extract for six weeks. 

Data from the current study revealed that the extract lowered the toxic effect of oxaliplatin on the testicular tissue samples. This was evident by the significant rise in the serum of total & free testosterone and CD4 cells, and the levels of GSH, SOD and CAT activities in the testis coupled with a marked reduction of serum TNF-α and IL-1β and testis MDA, nitric oxide levels and DNA fragmentation. Also, the extract promoted the regeneration of the histopathological structure of the testis. 

This study proposes a novel therapeutic application for the Costus extract as a therapeutic agent against testicular toxicity induced by oxaliplatin treatment through its promising anti-inflammatory and antioxidant properties.

Tert-butyl mercaptan is one of the frequently used odorants derived from natural gases. It has been declared as a health hazard by the Occupational Safety and Health Administration (OSHA) in the USA. There is not much information available about the mercaptans long-term toxicity secondary to occupational exposure. This study was conducted to evaluate the oxidative stress caused by mercaptan odorant. 

The inhalation exposure of 80 maintenance workers in a gas industry was evaluated, using NIOSH 2542 and samples analyzed by gas chromatography mass spectroscopy. Also, the administrative staff were selected as the unexposed workers with matching age and work experience compared to the exposed subjects. The lipid peroxidation and ferric reducing plasma ability (FRAP), was evaluated as oxidative stress biomarkers. The acetylcholinesterase activity was also assessed for the neurological risks.

The tert-butyl mercaptan exposure was evaluated at average 0.01 ppm (0.005 to 0.15 ppm). There was oxidative stress in maintenance workers along with a significant increase in the lipid peroxidation, and a decrease in FRAP level (P=0.0001). The acetyl cholinesterase activity was decreased in over half of the exposed subjects, and correlated significantly with the tert-butyl mercaptan level (r=-0.4, P=0.026).

There was a correlation between the inhibition of acetyl cholinesterase activity and the induction of oxidative stress. Based on the findings, the chronic occupational exposure to tert-butyl mercaptan was identified as a health hazard. Therefore, specific health care strategies should be developed to minimize the toxic effect of this chemical.

Caseous Lymphadenitis (CLA) is an important bacterial disease in goats, caused by Corynebacterium pseudotuberculosis. The disease is highly prevalent worldwide and causes significant economic losses to the cattle industry. Currently, the treatment of this disease with antibiotics remains largely unsuccessful due to the nature of the bacteria and the resultant resistance to the drugs.

Thirty apparently healthy female BALB/c mice, aged 5-6 weeks old were used to assess the efficacy of oxytetracycline loaded in calcium carbonate nanoparticle (OTC-CS-CaCO3NP) and toxicity of calcium carbonate nanoparticle (CS-CaCO3NP). The mice were randomly divided into five groups of six each and were exposed to the following treatments: Group 1: received sterile distilled water; Group 2: received 0.2 ml C. pseudotuberculosis; Group 3: received 0.2 ml C. pseudotuberculosis and 10mg/kg OTC; Group 4: was given 0.2 ml C. pseudotuberculosis and 10mg/kg OTC-CS-CaCO3NP; and Group 5: was administered 20mg/kg CS-CaCO3NP. 

The clinical signs of infection with C. pseudotuberculosis in the mice were significantly reduced after treatment with OTC-CS-CaCO3NP. The haematology results showed an insignificant reduction in the mean RBC count, Hb and haematocrit levels in Group 2 (infected controls) compared to the mice treated with oxytetracycline loaded nanoparticles. The biochemical analyses revealed no significant changes among the treatment groups. No histopathological lesions were found in the organs of the mice, treated with 20mg/kg CS-CaCO3NP, suggesting the absence of toxicity in vivo.

The results from this study indicate the potentials of OTC-CS-CaCO3NP as becoming a nano-antibiotic formulation for the treatment of caseous lymphadenitis infection in mice.

Despite modern developments in its management, still major concerns remain about drug resistance in chemotherapy. Natural adjuvants combined with chemotherapy might be the answer. We examined the anti-cancer, anti-proliferative and synergistic effects of Sambucus nigra extract with cisplatin chemotherapy (CDDP) on MCF-7 and MDA-MB-231 human cancer cell lines.

MCF-7 and MDA-MB-231 cell lines were cultured in DMEM culture media, containing 10% FBS and 100 U/ml penicillin/streptomycin. The anti-proliferative activity of SNA, CDDP and their synergic doses were determined using MTT method. Next, the apoptotic, metabolic, and cellular resistance gene expressions were measured through real-time quantitative PCR technique. To show the apoptosis effects and to diagnose cellular damages, an annexin V/propidium iodide (AV/PI) kit and malondialdehyde level were performed, respectively.

The synergic doses of SNA and CDDP in MCF-7 were 1.25µM CDDP+1.25µM SNA and on MDA-MB-231 was 2.5µM CDDP+2.5µM SNA. The results of real-time PCR showed that SNA induced apoptosis, disrupted metabolic pathways and reduced cellular drug resistance. In addition, the combination of SNA with CDDP compared with CDDP alone was able to change the expression of these genes and increase the rate of MDA and apoptosis generation (P<0.05).

The outcomes of this investigation indicate that SNA, as a herbal supplement, may be a candidate for increasing the effect of CDDP therapy in the treatment of breast cancers. This synergy was not estrogen-dependent in the MDA-MB-231 cells, promoted apoptosis, cell damages, disorders of metabolism, and reduced the drug resistance in the cancer cells.

Diazinon (Dzn), an Organophosphorus (OP) pesticide, is extensively used in agriculture. Acetylcholinesterase inhibition is linked to OP toxicity, and there are major mental health concerns associated with the use of pesticides. The objective of this study was to assess the depressive behavior in an animal model following their exposure to Dzn and the effect on the Brain-Derived Neurotrophic Factor (BDNF) as a critical neurotropic factor.

Male Swiss mice (N=42; 25±3g each) were used and their behaviors were eamined on including the locomotor, Forced Swimming (FST), and Sucrose Preference (SP) tests. These tests were performed the day after a single daily Dzn administration by gavage (2.5-20 mg/kg). Specific animal groups were exposed to Dzn daily (2.5-10 mg/kg) for 14 days, and a test was performed on days 7 and 15.

Following the acute exposure to Dzn, the animals’ locomotor activity did not change significantly. During the FST, Dzn at 20 mg/kg significantly increased the animals’ immobility time, indicating despair behavior. Imipramine, injected intraperitoneally at 10 mg/kg, did not cause the depressive behavior. The subacute exposure to Dzn induced less locomotor activity than that of the controls. The 7-day exposure to Dzn at 10 mg/kg significantly prolonged the immobility period compared to that of the controls. The 14-day Dzn exposure at 2.5, 5, or 10 mg/kg increased the immobility time significantly compared to that of the controls. None of the treatment groups showed SP, clearly showing animal anhedonia. The BDNF levels significantly decreased not only by subacute exposures to Dzn but also following a single exposure to this this pesticide.

The acute and subacute exposure to Dzn induced depressive behavior and increased the BDNF levels in the hippocampus of Swiss male mice following exposure to Dzn at varying doses of 2.5, 5, or 10 mg/kg.

Glyphosate is the most widely used herbicide, and it poses numerous health risks to the environment and living organisms. This study aimed at assessing the protective role of Adansonia digitata (A. digitata) on glyphosate-induced hepatorenal toxicity in a Wistar rat model.

Twenty-five rats were randomly divided into five groups of five animals each. The first group did not receive glyphosate and served as the control group. The second group received a single daily dose of only glyphosate (375 mg/kg). The treatment groups 3 and 4 were given a single daily dose of glyphosate (375 mg/kg) together with 250 mg/kg and 500 mg/kg of A. digitata extract, respectively. Group 5 was administered glyphosate (375 mg/kg) with Ascorbic Acid (200 mg/kg) as a comparison. At the conclusion of the study, blood serum samples from the rats were used for biochemical analysis. Then, the liver and kidneys were removed for histological examinations.

In comparison to the control rats in group I, those in group 2 that were given glyphosate had increased liver enzymes biomarkers, urea, creatinine and malondialdehyde levels, but their superoxide dismutase, catalase, and glutathione peroxidase levels decreased (P<0.05). Groups 3 and 4 rats that received fruits of A. digitata did not show the upsurge of liver enzymes biomarkers creatinine, urea and malondialdehyde. Furthermore, the extract of the fruits increased endogenous antioxidant biomarkers. A. digitata protected the glomeruli from degeneration and prevented histological liver steatosis.

This study’s findings suggest that the pre-treatment of rats with A. digitata extract provides a hepatorenal protective effect against glyphosate toxicity.

Oxidative stress has been shown to be an important factor, which plays a significant role in the pathogenesis of neurodegenerative disorders. Heat Shock Protein-27 (HSP-27) has been implicated in antioxidant responses against oxidative stress. Trehalose is a natural disaccharide widely used in a variety of food products with demonstrated protective effects against several neurodegenerative diseases. This study investigated the effects of trehalose on antioxidant responses, and the gene expressions for HSP-27 and caspase-3 against hydrogen peroxide (H2O2) induced oxidative injury in PC-12 cell line. 

The PC-12 cells were treated with various concentrations of H2O2 and trehalose for 24hr. The cell viability was assessed, using MTT and Lactate Dehydrogenase (LDH) release assays. Moreover, the activity of Catalase (CAT) and Glutathione Peroxidase (GPx) enzymes, and the Malondialdehyde (MDA) levels were determined. In addition, the levels of HSP-27 and caspase-3 gene expressions were measured. 

The results indicated that the pretreatment with trehalose increased cell survival against the H2O2-induced oxidative injury. Furthermore, trehalose elevated the CAT and GPx activities and reduced MDA levels compared to that of control group (P˂0.05). Moreover, trehalose upregulated the HSP-27 gene expression, while reducing the expression of caspase-3 gene compared to that of the untreated cells (P˂0.05). All of these biochemical changes were found to be dose-dependent for trehalose. 

Based on the study findings, trehalose had the capacity to attenuate the oxidative stress and cell injury. Therefore, trehalose may be suggested as a therapeutic agent to treat neurodegenerative disorders caused by oxidative stress damages.