Mohammad Karami

Hepatoprotective, antinociceptive and antioxidant activities of cimetidine, ranitidine and famotidine as histamine H2 receptor antagonists

The antioxidant, antinociceptive and hepatoprotective effects of H2 receptor blockers were examined with different experimental models. Antioxidant activities were determined by employing various in vitro assay systems such as 1,1‐diphenyl‐2‐picryl hydrazyl (DPPH) radical‐scavenging activity assays, reducing power determination assays, nitric oxide‐scavenging activity assays and hydrogen peroxide‐scavenging activity assays. Antinociceptive effects were determined using the hot plate test in mice. The hepatoprotective effects of cimetidine, ranitidine and famotidine against hepatotoxicity induced by carbon tetrachloride (CCl4) were determined by measuring the levels of serum enzymes alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities in mice. We found that the IC50 values of cimetidine, ranitidine and famotidine on DPPH radical‐scavenging activity were 671 ± 28, 538 ± 21 and 955 ± 43 μg/mL, respectively. Famotidine showed very strong nitric oxide‐scavenging activity. All three compounds showed very weak hydrogen peroxide‐scavenging activity. Moreover, the compounds did not exhibit any reducing power activity until concentrations of 1.6 mg/mL. All compounds also showed a dose‐dependent and marked analgesic activity in mice relative to controls. Pretreatment of mice with cimetidine, ranitidine or famotidine for three consecutive days reduced CCl4‐induced hepatotoxicity in mice. Treatment with 200 mg/kg ranitidine reduced AST, AST and ALP serum levels, while 200 and 40 mg/kg of cimetidine and famotidine, respectively, reduced AST and ALP serum levels. H2 blockers exhibited varying levels of antioxidant activities in various assays. Our results indicate that the antioxidant activities of H2 blockers have an analgesic activity and protective effect on CCl4‐induced hepatotoxicity in mice. These effects were greater with ranitidine than with the other compounds.

Antinociceptive Activity and Effect of Methanol Extracts of Three Salvia Spp. on Withdrawal Syndrome in Mice

PURPOSE There are several reports about effects of Salvia spp. on CNS. The present experiment is undertaken to study effect of S. limbata, S. hypoleuca and S. macrosiphon on withdrawal syndrome in mice. METHODS Antinociceptive activities of aerial parts of Salvia spp. is investigated using hot plate method. In addition, the effect of its aerial parts on morphine dependence is investigated in mice. After induction of morphine dependency, different concentrations of plant extract are injected. To assess morphine withdrawal, naloxone (5 mg kg-1, i.p.) are injected into mice on the 5th day. Withdrawal syndrome is assessed by placing each mouse in a glass box 30 cm in height and recording the incidence of escape jumps for 60 minutes. RESULTS A decrease in incidence of escape jumps is observed in morphine dependence mice. S. limbata and S. hypoleuca extracts produced a statistically significant inhibition of pain induced by hot plate latency at (500, 1000 and 1500 mg kg-1) i.p. A significant increase in pain threshold is observed after 30 and 60 minutes (p < 0.001). The activity was comparable to that of morphine (30 mg kg-1, i.p., p > 0.05). The antinociceptive activity increased up to 60 minutes. CONCLUSION S. limbataand S. hypolecuca extracts produced statistically significant inhibition of pain and development of morphine dependence in mice.

The effect of epicatechin on oxidative stress and mitochondrial damage induced by homocycteine using isolated rat hippocampus mitochondria

Oxidative stress and mitochondrial dysfunction are the main suggested mechanisms for neurodegenerative diseases. In this study, we have evaluated the effects of epicatechin (EC) on mitochondrial damage induced by homocycteine (Hcy) using isolated rat hippocampus mitochondria in vivo. EC (50 mg/kg) was gavaged daily for a period of 10 days, starting 5 days prior to Hcy (0.5 μmol/μL) intra hippocampus injection in rats. Mitochondria were isolated from brain by different centrifuge techniques. Mitochondrial function was assayed by MTT test. Also, mitochondrial swelling and oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation and glutathione (GSH), were assayed. Hcy induced mitochondrial dysfunction and swelling. Increase in ROS formation, lipid peroxidation, and decreased GSH were observed after Hcy treatment in isolated brain mitochondria. Furthermore, oral administration of EC significantly decreased the lipid peroxidation and ROS levels and also increased GSH levels. Also, EC treatment significantly improved mitochondrial function. As EC indicated protective effects against oxidative stress and mitochondrial damage induced by Hcy, it is suggested for further trials for prevention or treatments of neurodegenerative disorders such as Alzheimer disease.

Protective effect of thymoquinone against diazinon-induced hematotoxicity, genotoxicity and immunotoxicity in rats

Several studies have shown that oxidative stress and cell damage can occur in the very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin) against DZN immunotoxicity, hematotoxicity and genotoxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups, (eight per group) as follows: control (receiving corn oil as the DZN solvent), DZN (20mg/kg), Thy (10mg/kg), Thy (2.5mg/kg)+DZN, Thy (5mg/kg)+DZN and Thy (10mg/kg)+DZN. After four weeks of treatment, the hematological parameters of red blood cells (RBCs), white blood cells (WBCs), hemoglobin (Hb), hematocrit (Hct) and platelets (PLTs) were evaluated. The evaluation of genotoxicity was carried out using the micronucleus assay. For measurement of cytokine production, interferon gamma (IFN-γ), interleukin 10 (IL10) and interleukin 4 (IL4) were chosen as immunotoxicity indicators of DZN toxicity. DZN was found to decrease RBCs, WBCs, Hb, Hct, PLTs, butyrl- and acetyl-cholinesterase activity and I FN-γ and increased the micronucleus indices of IL10 and IL4 as compared with the control group. Treatment with Thy reduced DZN hematotoxicity and immunotoxicity, but, significantly, did not prevent genotoxicity. This study showed that Thy (without the significant effect on genotoxicity) decreased the hematological toxicity, immunotoxicity and butyrl and acetyl cholinesterase activity induced by DZN. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents.

Incidentally Solitary, Synchronous, Metastatic Left Adrenal Mass From Colon Cancer

The authors report the case of a 63-year-old man who underwent an open adrenalectomy for a synchronous, malignant, metastatic left adrenal tumor and a total colectomy for T3N0M1 (stage 4) primary, malignant colon cancer. Two polypoid lesions, one measuring 40 mm × 30 mm × 30 mm and the other measuring 20 mm × 10 mm × 10 mm, were found in the ascending colon and rectosigmoid (RS) junction, respectively, and a synchronous, malignant, left adrenal gland lesion measuring 70 mm × 50 mm × 30 mm was incidentally found on abdominal computed tomography scan. Histological examination revealed a metastatic, necrotic adenocarcinoma of the left adrenal mass, an adenocarcinoma of the cecal mass, and an adenomatous polyp (tubulovillous type) of the smallest polypoid lesion in RS junction that had invaded deeply into the submucosal layer. The patient recovered uneventfully, and his condition is now stable, with no evidence of local recurrence or metastatic disease, 2 years after the surgery. To the best of our knowledge, only 25 cases of an adrenalectomy for treating metastatic adrenal gland tumors have been reported to date; physicians should be aware of the possibility of this event.

A importância do controle da temperatura corporal materna após injeção de meperidina durante a raquianestesia em pacientes submetidas à cesariana: uma sugestão para conduzir estudos clínicos

Shivering related to spinal and epidural anesthesia is distressing to parturient women as it may cause cardiovascular and metabolic disturbances. Shivering increases cardiac output and causes tachycardia; also, hypothermia-induced shivering increases total body oxygen consumption and could cause hypoxemia. These effects may place mothers and the fetuses at the greatest risk during delivery. The rate of shivering varied from 36% to 55% in different studies. Meperidine is a (Kappa)-receptor agonist and opioid (Mu) receptor that reduces the threshold of vascular constriction and is known to treat shivering effectively. Here we provide comments on three points on the importance of body temperature recording after injection of meperidine, based on clinical research conducted on patients undergoing spinal anesthesia for cesarean section. First, intra-operative shivering is a particular feature of thermoregulation in awake patients undergoing regional anesthesia (in response to sympatholysis, vasodilatation and increased heat loss). Intra-operative shivering is inhibited during general anesthesia; accordingly patients are more prone to hypothermia and post-operative shivering. Hence, there are two important elements to regional anesthesiainduced shivering: (1) the desired effect of shivering, i.e., heat preservation by increased basal metabolic rate and (2) the unwanted effects of shivering (increased venous O2, desaturation, myocardial O2 extraction, discomfort and anxiety for patient, and possibly movement for surgeon and monitoring artifacts for the anesthesiologist (e.g., systolic pO2, noninvasive blood pressure and ECG artifacts in intra-operative shivering). Therefore, the authors should measure maternal body temperature to assess the desired effects. Second, whenever volume pre-loading with 10 mL/kg or 15 mL/kg of room temperature crystalloid is employed, the maternal hypothermia could reasonably be expected to alter shivering prevalence. Therefore, maternal temperature recording is very important. Third, if meperidine suppresses shivering, it may lead to lower body temperature following regional anesthesia and this may lead to more hypothermia and also to more shivering later on. Accordingly, appropriate body temperature recording after injection of meperidine during spinal anesthesia in patients undergoing cesarean section should be considered by authors in future studies for more accurate and reliable findings.

Hepatoxicity of aqueous extract and fractionated methanol extract of Phytolacca americana by isolated rat liver perfusion system

Recombinant retroviral vector containing human tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) gene was constructed and investigation of the in vitro invasion and metastasis of gastric cancer cells transfected with TIMP-2 was carried out. Human TlMP-2 was isolated from recombinant vector Bluescript 1/TIMP-2(+), and then inserted into the retroviral vector pL-MT. Correct orientation was verified by restriction endonuclease digestion. Human full length TIMP-2 gene was ligated into a plasmid, which was then transfected into PA317 cell line. G418-resistant individual clones were selected to transfect human SGC-7901 cell line. Cell proliferation, cell electrophoresis, soft agar colony formation and in vitro invasion were detected to analyze the bio-behavioral changes of cancer cells. The results from restriction endonuclease digestion were as theoretically expected. The cell electrophoresis rate, colony number and invasion ability in SGC-7901 cells and MFC cells transfected with TIMP-2 gene were significantly decreased when compared with control group. However, no significant changes were noted in the proliferation of cancer cells. We successfully construct a recombinant retroviral vector containing human TIMP-2. TIMP-2 transfection could markedly alter the membrane charge of cancer cells, resulting in decreased electrophoresis capacity, cell migration and invasion. However, cell growth was not affected by TIMP-2. These results suggested TIMP-2 transfection might exert effects on the malignant phenotype of cancer cells through affecting extracellular environment, which provided a new way to investigate gene regulation of in vitro collagen metabolism.

Protective effect of thymoquinone, the main component of Nigella Sativa, against diazinon cardio-toxicity in rats

Abstract Several studies have shown that oxidative stress and cell damage can occur at very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin), against DZN cardio-toxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups: control (corn oil gavages), DZN gavages (20 mg/kg/day), Thy gavages (10 mg/kg/day) and Thy + DVN gavages (2.5, 5 and 10 mg/kg/day). Treatments were continued for 28 days, then the animals were anesthetized by ether and superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), lactate dehydrogenize (LDH) and glutathione peroxide (GPX) activity was evaluated. In addition, glutathione (GSH) and malondialdehyde (MDA) the heart tissue and creatinephosphokinase-MB (CPK-MB) and troponin (TPI) levels and cholinesterase activity in the blood were evaluated. DZN-induced oxidative damage and elevated the levels of the cardiac markers CK-MB, TPI, MDA and LDH and decreased SOD, CAT and cholinesterase activity and GSH level compared with the control group. Treatment with Thy reduced DZN cardio-toxicity and cholinesterase activity. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents. Administration of Thy as a natural antioxidant decreased DZN cardio-toxicity and improved cholinesterase activity in rats through the mechanism of free radical scavenging.

Effects of aqueous methanolic extract of Salvia limbata on antinociceptive activity and withdrawal syndrome in mice

It is quite clear that the repeated use of opioid drugs leads to physical dependence and tolerance. Dependence can be measured by evaluation of self-restraint signs from abrupt drug withdrawal or administration of a narcotic antagonist or both. Effects of some Salvia genesis , of Salvia aerial parts extract on morphine dependence were investigated in mice. After induction of dependence by morphine, distilled water was injected into the control group and different concentrations of plants aerial extract were injected into the other five groups. To assess morphine withdrawal, mice were injected with naloxone (5 mg/kg) intraperitoneally (i.p.) on the 5th day. After four consecutive days of morphine injection, withdrawal syndrome was assessed by placing each mouse in a 30 cm high glass box and recording the incidence of escape jumps for 60 min. Animal receiving acute treatment with morphine displayed dependence. The animals treated with different Salvia limbata aerial (flowered browse) parts extracts concentration decreased incidence of escape jumps in number or decreased development of morphine dependence and on the other hand, addiction was observed following naloxone administration (P 0.05). The anti-nociceptive activity of S. limbata increased until the 60th min as compared to morphine (P<0.05). Key words : Morphine dependence, anti-nociceptive activity, Salvia limbata, jumping, hot plate method.