Iranian Journal of Toxicology
Volume:17 Issue: 2, May 2023

Diabetes is one of the most prevalent endocrine disorders in humans, and its first-line medication is metformin. Peroxisome proliferator-activated receptor gamma (PPAR–γ) agonists are the adjuncts to metformin. Bavachinin is a PPAR pan-agonist with fewer side effects than metformin" into PPAR–γ agonists. In this study, the synergistic effects of metformin and Bavachinin were investigated on type II diabetic rats.

After four weeks of a high fat and glucose diet, type II diabetes was induced in 28 male Wistar rats, using injection of streptozotocin and nicotinamide. The animals were distributed into five groups of seven each: 1) Normal control (N), 2) Diabetic control (D), 3) Diabetic rats receiving metformin (DM), 4) Bavachinin (DB), and 5) Metformin plus Bavachinin (DMB). Oral glucose tolerance test (OGTT), fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of β-cell function (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR), and insulin sensitivity index (ISI) were obtained.

The OGTT results in DM, DB, and DMB groups were significantly improved compared to that of D group. The FBG levels were significantly lower in DMB than in DB, DM, and D groups. The FINS levels of DMB were significantly less than those of DB, DM, and D groups. The HOMA-IR and HOMA-β were comparable between DMB and N groups. The ISI improved significantly in DMB compared to those in DM, DB, and D groups.

Bavachinin may be used combined with metformin for the treatment of type II diabetes at lower doses of metformin, thus having fewer side effects.

Isoproterenol, a β-adrenergic agonist, may induce myocardial infarction when used in high dosage in rats. This study was conducted to evaluate the effect of the ethanol extract of Kleinhovia hospita leaves on cardiac biomarkers and myocardial structures of rats induced by isoproterenol.

Male rats (n=30) were assigned as a normal controls or treatment groups. The treatment groups received pretreatments, either placebo or the extract at doses of 250, 500, or 750 mg/kg for 14 days, followed by two isoproterenol injections at 100 mg/kg. After 24 hours, blood samples were taken and the hearts dissected. The tested cardiac biomarkers were creatinine kinase myocardial band (CKMB) and lactate dehydrogenase (LDH). Heart histopathology analysis was performed followed by staining of samples with hematoxylin and eosin.

The isoproterenol injections significantly increased CKMB and LDH levels in the placebo group compared to those in normal controls. Pretreatment with the extract at doses of 500 and 750 mg/kg significantly reduced the serum CKMB and LDH levels compared to those of the placebo. The histopathological examinations showed the presence of diffused necrosis and severe inflammation in the placebo group. Pretreatment with the extract at 500 or 750 mg/kg significantly reduced the myocardial tissue damages in rats.

The K. hospita extract at doses of 500 or 750 mg/kg significantly reduced the infarctions in the rats’ heart tissue, shown by significantly low levels of CKMB and LDH, and reduced necrotic lesions and inflammation in the rat heart tissue samples induced by isoproterenol pretreatment.

The plant Bombax costatum (BC) has been used traditionally in Nigeria for the management of various ailments. The chloroform extract of BC bark was investigated for its potential effects against the induced seizures and depression in rats.

Thirty Wistar rats were divided into five groups of six. Group I received normal saline, group II received pentylenetetrazole (PTZ, 35 mg/kg), group III received diazepam (5 mg/kg) plus PTZ at 35 mg/kg, group IV received 250 mg/kg of the BC extract, and group V received 500 mg/kg of the same extract. The above protocol was repeated on alternate days from the first to twenty 5th days. 

Tukey’s post hoc test revealed a statistically significant increase in the seizure scores after using PTZ (3.38±0.29, P<0.0001), in contrast to a decrease in the seizures after treatment with the BC extract (250 mg/kg; 2.72±0.25, P=0.0001). The analysis of variance for forced swimming test showed a significant decrease in immobility time if treatment with the extract (250 mg/kg; 125±5.59; P=0.01). The immobility duration increased with the PTZ treatment (163.8±12.03). The brain’s dopamine and serotonin levels under PTZ effect significantly decreased to 140.2±15.66 and 26.38±1.16, respectively, when the rats were treated with the extract at 500 mg/kg. 

The findings of this study suggest that the BC extract has anticonvulsive and anti-depressive properties, thus it offers neuro-protection against both conditions, induced by PTZ in rats.

Membrane technology for water purification has gained much attention in many industries and for healthier human life. Also, improving the elimination of toxic heavy metals is a much needed strategy for the filtration of public water supplies. This study investigated the removal of toxic heavy metals from wastewater, using a novel thin-film membrane.

We investigated the structural, physico-chemical, and antifouling properties of the membrane, and its ability to remove toxic elements from water. Seven parameters were examined: Contact angle, water ionic contents, Fourier’s transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), 3D-surface imaging, water flux, and antifouling effects.

The results indicated that a thin-film layer formed on the membrane. The 3D-images demonstrated that the surface roughness decreased when the polyaniline ratio to nanoparticles increased. The surface hydrophilicity increased by incorporating polyaniline into the surface. The water flux increased from 8.04 (L/m2.h) to 14.74 (L/m2.h) in the virgin membrane. The sodium sulfate rejection was 61% for the virgin membrane whereas it was >67% in the thin-film coated membrane. The data demonstrated excellent anti-fouling properties for the novel membrane, with a flux recovery ratio of >94.65% while it was about 79% for the virgin one. The rejection rates of chromium and copper ions for the novel membrane were >86% and >84%, respectively. These values were significantly higher than those of the virgin membrane (>53% and >51%). 

The thin-film composite membrane significantly improved the removal rate of toxic heavy metals from the wastewater samples compared to the virgin membrane.

The effect of Astragalus has been recognized in traditional Chinese medicine, and the roots are believed to have anti-cancer properties. This study investigated the effects of the ethanolic extract and polysaccharide fraction of Astragalus ovinus roots on MCF7 cell line.

We used MTT assay to evaluate the cytotoxicity of A. ovinus roots. The status of cell cycle and apoptosis were examined, using flow cytometry. The gene expressions related to the extrinsic and intrinsic apoptotic pathways (caspases 8 & 9) were also examined by real-time polymerase chain reaction (PCR). 

The cytotoxicity data showed that the A. ovinus extract inhibited the proliferation of MCF7 cancer cells in a dose-dependent manner. The IC50 of Cisplatin , ethanolic extract and polysaccharides fraction were 22.42, 560.9, and 961.2 in µg/ml, respectively. Also, the cell cycle analysis showed that the ethanolic extract and polysaccharide fractions arrested the cell cycle in the G1 phase. Examination of the apoptotic effects showed that treatment with either the A. ovinus extract or the polysaccharide fraction induced apoptosis in MCF-7 cancer cells. The expression of caspases 8 and 9 genes was inhibited after exposure to either cisplatin or the polysaccharide fraction (PFA). However, treatment with the extract inhibited only the caspase-8 gene expression.

The results confirmed that treatment with the extract and polysaccharide fraction caused anti-proliferative effect and apoptosis of MCF-7 cell line. Therefore, it can be concluded that the A. ovinus extract and the polysaccharides have potential therapeutic effects against human breast cancer cells.

Celosia leptostachya belongs to Amaranthaceae plant family. Its leaves are used traditionally in the treatment of conditions, such as convulsion, eye infection and most notably to cure snakebites. This study investigated the inhibiting effect of the extract of C. leptostachya leaves against cobra snake venom in mice.

We used 36 albino mice of mixed gender, weighing 20-25 g. They were divided into six groups of six rats each. Each rat was pre-treated with 0.4 mg/kg of cobra snake venom, and was subsequently given a graded dose of zero, 50, 100, 150, 200, or 250 mg/kg of the ethanol extract of C. leptostachya leaves. The animals were monitored for the survival rate. Various inhibition assays were performed to estimate the activities of acetyl cholinesterase, protease and adenosine triphosphatase of cobra venom, in the presence of 100-300 µg of the plant extract.

The extract inhibited the effects of cobra venom significantly after the intraperitoneal injection of the venom and extract at 20 minutes intervals. The results demonstrated that 100% of the mice survived if they received 100-250 mg/kg of the extract while only 83.3% survived with the extract at 50 mg/kg. The extract inhibited the venom’s acetyl cholinesterase, protease and adenosine triphosphatase. The inhibition occurred at higher percentages if the extract was given at 300 mg/kg. 

The plant extract significantly inhibited the snake venom, and its acetyl cholinesterase, protease and adenosine triphosphatase that mediated the venom’s toxicity.

Alcohol abuse contributes to the pathology of gastric ulcers. The tissues contain antioxidants, but the activity declines when exposed to reactive oxygen species. The Ammi visnaga extract has substantial scavenging effects and is rich in phenols and flavonoids. We estimated the gastro-protective and antioxidative effects of A. visnaga extract on rats’ gastric mucosal lesions after exposure to ethanol.

Forty adult male albino rats were divided into four groups of ten each. Group 1 (standard control), group 2 received omeprazole 20 mg/kg+1 mL ethanol, group 3 (ulcer model) received 1 mL ethanol 80% only, and group 4 received 1200 mg/kg/day A. Visnaga extract+1 mL ethanol 80%. The gastric pH, percentage of ulcer area, gastric mucus secretion, oxidative and antioxidant markers, and histopathology were examined in each group.

Pre-treatment with omeprazole and A. visnaga extract improved the gastric acidity, the ulcerated areas, and the gastric mucus secretion compared to the rats in group 3. Compared to group 3, rats treated with omeprazole and A. visnaga extract showed major improvements in the tissue glutathione, superoxide dismutase, and catalase levels. The histopathology examinations showed ulceration of the glandular mucosa in group 3, accompanied by multifocal inflammatory cell infiltrations. The omeprazole treatment completely protected the gastric mucosa in group 2. Significant improvement was also observed in rats pretreated with A. visnaga extract (group 4).

The gastro-protective effects of A. visnaga extract included the inhibition of tissue oxidative stress and increased the antioxidant properties.

Drugs are the mainstay of the clinical management of epilepsy. Carbamazepine (CBZ) is commonly used for treating epilepsy and neuropathic pain. This drug has been reported to have toxic effects on the hematological system due to its induction of oxidative stress. This study aimed to investigate the protective effects of vitamin C against hematological and thyroid toxicities caused by the chronic use of carbamazepine in male Wistar rats.

Thirty-two adult Wistar rats were categorized randomly into four groups of eight rats each and treated as follows: Group 1 received distilled water (2 mL/kg); group 2 was treated with vitamin C (100 mg/kg); group 3 received carbamazepine (20 mg/kg), and group 4 was pre-treated with vitamin C (100 mg/kg) and given carbamazepine (20 mg/kg) 30 min later. All treatments were administered via gavage once per day over fifteen consecutive weeks. The rats’ blood samples were tested for changes in hematological parameters while the sera were evaluated for liver biochemical enzymes and thyroid hormone levels.

The results revealed that pre-treatment with vitamin C protected against alterations in parameters associated with hematological and thyroid toxicities. 

Based on the study results, it was concluded that: a) The chronic use of CBZ caused hematological and thyroid toxicities, and b) Vitamin C protected against these toxicities. Therefore, it is highly likely that vitamin C has the potential to protect experimental animals against injuries induced by CBZ to the liver, blood cells, and hypothalamic-pituitary-thyroid axis in a Wistar rat model.