Effects of tramadol administration on male reproductive toxicity in Wistar rats The role of oxidative stress, mitochondrial dysfunction, apoptosis-related gene expression, and nuclear factor kappa B signalling.

AIM: The present study investigated the role of redox balance, inflammation, mitochondrial dysfunction, and apoptosis in Tramadol (Tra)-induced testicular toxicity. METHOD: Twenty-four male Wistar rats were randomly divided into either the control group or the groups receiving different doses of Tra (25, 50, and 75 mg/kg/day, i.p.) for 21 successive days. Testicular tissues were collected for oxidative stress, mitochondrial function, sperm assays and histopathological evaluation. Real-time polymerase chain reaction was performed to evaluate the markers of inflammation and apoptosis. RESULTS: Tra caused a significant reduction in the sperm count, motility and morphology, while it caused a marked increase in oxidative stress parameters. In addition, Tra induced testicular mitochondrial dysfunction due to the collapse of mitochondrial membrane potential and mitochondrial swelling. It also led to the significant inhibition of anti-apoptotic Bcl-2 expression, besides a significant increase in pro-apoptotic Bax expression. There was a significant increase in the level of tumour necrosis factor-α, interlukin-1ß and nuclear factor kappa B. Histopathological degenerative changes were observed in the testis after Tra exposure. CONCLUSIONS: The present results suggest that Tra exposure may lead to reproductive toxicity due to the loss of the antioxidant defence system, mitochondrial dysfunction, and activation of inflammatory and apoptotic pathways (Tab. 4, Fig. 5, Ref. 63).

Frequency Evaluation of T6235C (m1) and A4889G (m2) Polymorphisms of CYP1A1 Gene in a Healthy Population from the west of Mazandaran Province, Iran.

CYP1A1 is an important phase I xenobiotic metabolizing enzyme involved in the metabolism of numbers of toxins, endogenous hormones and drugs. Polymorphisms in this phase I gene can alter enzyme activity and induction, also are known to be associated with cancer susceptibility related to environmental toxins and hormone exposure. The present study was aimed to determine the frequencies of commonly known functional polymorphismsof CYP1A1 gene including CYP1A1 m1 (MspI), and CYP1A1 m2 (Ile-Val) in a healthy population from the west of Mazandaran province, Iran. A total of 200 unrelated healthy subjects from Mazandaran province, residing in Tonekabon city, coming for blood donating at Tonekabon Blood Transfusion Center were enrolled. Genomic DNA was extracted from peripheral blood lymphocytes of each subject. All subjects were genotyped for CYP1A1 m1 (T>C) and m2 (A>G) by polymerase chain reaction-restriction fragment length polymorphism method. The frequencies of the TT(wt/wt), TC(wt/mt) and CC(mt/mt) genotypes were as 65.5%, 32.0% and 2.5% respectively for m1 and frequencies of the AA(wt/wt), AG(wt/mt) and GG(mt/mt) genotypes were as 84.5%, 15% and 0.5% respectively for the m2. The frequencies of T and C alleles in the population were 81.5% and 18.5% respectively and the frequencies of A and G alleles were 92% and 8% respectively. Results of the present study might be important in understanding the distribution of CYP1A1 (m1) and CYP1A1 (m2) polymorphisms in Mazandaran province of Iran. Moreover, these results may determine the susceptibilities of individuals towards environmental procarcinogens that result in several cancers.

Potential chemoprotective effects of selenium on diazinon-induced DNA damage in rat peripheral blood lymphocyte.

The purpose of this study was to investigate the protective effects of selenium (Se) against genotoxicity induced by diazinon (DZN) in rat peripheral blood lymphocytes by micronucleus (MN) test. Animals were concurrently administered intraperitoneally with DZN in proper solvent (20 mg/kg body weight (b.w.)) and Se at three different doses (0.5, 1, and 2 mg/kg b.w.) for 30 consecutive days. The positive control group received DZN at the same dose without Se. After 24 h of last injection, 0.5 ml blood of each rat was received and cultured in culture medium for 44 h. The lymphocyte cultures were mitogenically stimulated with cytochalasin B to allow the evaluation of number of MNs in cytokinesis-blocked binucleated cells. Incubation of lymphocytes with DZN induced additional genotoxicity and is shown by increase in MNs frequency in human lymphocytes. Se at low dose of 0.5 mg/kg had a maximum effect and significantly reduced the MNs frequency in cultured lymphocytes (p < 0.0001) that reduced the frequency of MN from 12.78 ± 0.24% for DZN group to 4.40 ± 0.36. The present study revealed that Se particularly at low doses has a potent antigenotoxic effect against DZN -induced toxicity in rats, which may be due to the scavenging of free radicals and increased antioxidant status.

Anticonvulsant activity of Hypericum scabrum L.; possible mechanism involved.

OBJECTIVES: Hypericum (H.) spp. has been used in traditional medicine for their anticonvulsant effect for many years. In spite of many works on this genus, little is known about H. scabrum. In this work, anticonvulsant activity of H. scabrum was investigated. MATERIALS AND METHODS: Anticonvulsant activity of aqueous extract was evaluated by pentylenetetrazole (PTZ) induced convulsion and picrotoxin induced convulsion. Also, nitric oxide radical scavenging was investigated as a possible mechanism involved. RESULTS: Extract (125-500 mg kg-1, i.p.) significantly delayed the onset of PTZ induced convulsion. At 500 mg kg-1, 100% protection against mortality was observed. At this dose, it significantly prolonged the onset of picrotoxin induced convulsion in mice, too. It showed significant nitric oxide radical scavenging activity. CONCLUSIONS: Mechanism of anticonvulsant activity may be through GABA and/or nitric oxide pathway.

Cytotoxicity of hydro-alcoholic extracts of Cucurbitapepo and Solanum nigrum on HepG2 and CT26 cancer cell lines.

Plants are used worldwide for the treatment of diseases, and novel drugs continue to be developed through research from plants. There are more than 20,000 species of plants used in traditional medicines, and these are all potential reservoirs for new drugs. Cucurbitapepo has been used in traditional folk medicine to treat cold and alleviate ache. Previous pharmacological tests have shown that it possesses antiviral, anti-inflammatory, and analgesic effects. Also, Solanum nigrum has been used as a diuretic and an antipyretic agent and it has also been used to cure inflammation, edema, mastitis and hepatic cancer. In this investigation, cytotoxicity of specific concentrations of hydro-alcoholic extracts of C. pepo and S. nigrum was studied on normal [Chinese hamster ovarian cells (CHO) and rat fibroblast] and cancer (HepG2 and CT26) cell lines. The cytotoxic effects and IC(50) of the extracts on the selected cell lines were studied followed by colonogenic assay method. The results showed that IC(50) of S. nigrum extract was significantly lower than that of the C. pepo extract on all four cell lines (P < 0.05). On the other hand, IC(50) of S. nigrum extract was significantly higher than the extract of Taxus baccata and Cisplatin, herbal and chemical control positive anticancer compounds, respectively, on all four cell lines (P < 0.05). As a result, it is concluded that the extract of S. nigrum has almost similar cytotoxicity to the extract of T. baccata on cancer cells.

Comparison of the cytotoxic effects of Juniperus sabina and Zataria multiflora extracts with Taxus baccata extract and Cisplatin on normal and cancer cell lines.

Isolation and identification of some potent anti-tumor compounds from medicinal plants has motivated researchers to screen different parts of plant species for the determination of anti-tumor effects. In this study, cytotoxic effects and IC(50) of specific concentrations of hydro-alcoholic extracts of fruits of Juniperus sabina and leaves of Zataria multiflora were compared with hydro-alcoholic extract of bark of Taxus baccata and Cisplatin, well-known anticancer compounds, on normal (CHO and rat fibroblast) and cancer (HepG2 and SKOV3) cell lines. The hydro-alcoholic extracts of the plants were prepared by percolation. The cytotoxic effects and IC(50) of the extracts on the cell lines were studied followed by colonogenic assay after 72 h incubation. The results showed that the extract of Juniperus sabina possesses lower IC(50) in comparison with Zataria multiflora extract on all 4 normal and cancer cell lines (P<0.05); but, IC(50) of the Juniperus sabina extract was significantly higher than the Taxus baccata extract and Cisplatin on all 4 normal and cancer cell lines (P<0.05). As a result, it is concluded that the extract of J. sabina has almost similar cytotoxicity with the extract of Taxus baccata on cancer cells.