Volume 26, Issue 3

Background: The preclinical incision pain models and clinical studies in healthy volunteers have demonstrated the central serotonergic analgesic mechanism, paracetamol analgesia. This has been evidenced by raised serotonin concentrations in the brain following paracetamol administration in a few studies. The inhibition of paracetamol analgesia by 5-HT 3 antagonists suggests that this analgesia is 5-HT 3 mediated. However, in a few studies, 5-HT 3 antagonists themselves exhibited an analgesic action. Various studies in this context stated intricate results. The present study was intended to understand the pharmacodynamic interaction between paracetamol and ondansetron in postoperative patients. Methods: This randomized clinical trial included 32 postoperative cases of either sex, ages between 18 and 70 years. The patients were randomly allocated into the placebo and test groups and received respective treatment at the end of surgery. The pain score was recorded using Visual Analogue Scale (VAS) and Face, Legs, Activity, Cry, Consolability (FLACC) behavioral scale at awakening and every 30 min for the next 3 h. The postoperative rescue analgesic consumption for 24 h was recorded. The data were analyzed using OpenEpi and SciStatCalc statistical software. Results: A significantly higher pain score was observed in the placebo group postoperatively for 60 min on VAS (p<0.05 and p<0.01), whereas the FLACC behavior scale score was significantly higher at 120 and 150 min (p<0.05). The test group patients were more comfortable throughout the study, and the postoperative analgesic requirement was significantly lesser (p<0.05). Conclusions: The pharmacodynamic interaction between paracetamol and ondansetron coadministration does not block but instead increase paracetamol analgesia, reduce the postoperative analgesic requirement, and improve the postoperative comfort level.

Background: Mounting experimental evidence highlights the testicular and neuronal toxicity of environmental/industrial chemicals in experimental animals via the mechanism involving oxidative damage. Nigerian Bonny Light crude oil (BLCO) has been reported to exhibit reproductive and neuronal toxicity in male rats. Studies have shown that vitamin E and quercetin protect rat neuronal and testicular cells from environmental chemical-induced oxidative damage. We investigated the possible protective role of quercetin and vitamin E in BLCO induced-neuronal and testicular toxicity. Methods: Male rats were administered BLCO at doses of 400 and 800 mg/kg body wt/day p.o. three times/week for 6 weeks. Other groups were co-administered BLCO (400 and 800 mg/kg body wt/day p.o.) with/without vitamin E (50 mg/kg body wt/day p.o.) or quercetin (10 mg/kg body wt/day p.o.) three times/week for 6 weeks, respectively. Results: Semen quality deteriorated, testosterone and luteinizing hormone (LH) levels were significantly decreased, and follicle stimulating hormone (FSH) increased following BLCO reatment. There was a significant decline in the activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and glutathione-S-transferase (GST) with concomitant increased levels of lipid peroxidation and activities of xanthine oxidase (XO) in a dose-dependent manner, in testes and brain of rats. Co-administration with vitamin E or quercetin reversed BLCO-induced neuronal and testicular toxicity by preventing oxidative stress, improving sperm quality, and restoring hormonal levels relative to controls. Conclusions: BLCO altered reproductive indices and induced neuronal toxicity via the mechanism of oxidative stress. Quercetin and vitamin E showed possible chemoprotection against the toxicity.

Background: Numerous studies suggest that apelin plays a significant role in cardiovascular regulation and in the pathogenesis of hypertension. The purpose of the present study was to determine whether apelin-13 (AP-13) is involved in the regulation of cardiovascular responses to acute stress in spontaneous hypertension. Methods: The effects of intracerebroventricular (ICV) administration of AP-13 on changes in mean arterial blood pressure (MABP) and heart rate evoked by an alarming stress (air jet stress) were compared in awake normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The rats were divided into four groups: Groups 1 (WKY) and 3 (SHR) received ICV infusion of 0.9% sodium chloride (vehicle), whereas Groups 2 (WKY) and 4 (SHR) were ICV infused with AP-13. All animals were exposed to the alarming stress. Results: During the ICV administration of the vehicle, the pressor response to stress was significantly greater in SHR than in WKY. The ICV infusion of AP-13 reduced the pressor response evoked by the application of the stressor in SHR but not in WKY. It also abolished the difference in stress-induced MABP increases between WKY and SHR. Conclusions: The results show that centrally acting apelin may play an essential role in the regulation of blood pressure responses to an alarming stress in SHR rats.

Background: Sodium fluoride (NaF) intoxication is associated with oxidative stress and altered antioxidant defense mechanism. The present study was carried out to evaluate the potential protective role of blackberry and quercetin (Q) against NaF-induced oxidative stress and histological changes in liver, kidney, testis and brain tissues of rats. Methods: The rats were allocated evenly to seven groups. The first group was maintained as the control, whereas groups 2, 3, 4, 5, 6 and 7 were administered blackberry juice (BBJ), Q, NaF, BBJ+NaF, Q+NaF and BBJ+Q+NaF, respectively, for a period of 30 days. Results and conclusions: NaF caused an elevation in lipid peroxidation level paralleled with significant decline in glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase and catalase activities as well as the total antioxidant activity in liver, kidney, testes and brain. Some histopathological changes were detected in all tested tissues of the NaF treated group. Q and BBJ had successfully maintained normal histological architecture and mitigated the induction of oxidative stress caused by NaF. Q effectively reduced the elevation in thiobarbituric acid reactive substances level and restored the activities of antioxidant enzymes in liver, kidney, testis and brain. Less histopathological changes were observed in Q+NaF and BBJ+NaF treated groups. As a result, BBJ and Q significantly reduced NaF-induced oxidative and histological changes in rats. In the combination of BBJ and Q against NaF toxicity, the effects were more severe than from separate exposure, thus indicating that these flavonoids exhibited synergistic effects on all antioxidant and histological parameters.

Background: This work was designed to investigate the modulatory effects of cod liver oil on the acute exposure to carbon tetrachloride (CCL 4 ) in experimental animal models. Methods: Markers of oxidative stress, enzymic and non-enzymic antioxidants were assessed in the liver and kidney. Results: The results showed significant (p<0.05) increase in the total protein of the kidney of rats pretreated with cod liver oil compared to the control and CCL 4 -treated groups. Acute exposure to CCL 4 also significantly (p<0.05) increased thiobarbituric acid reactive substances in the liver of rats treated with cod liver oil compared to the CCL 4 -treated rats. The reduced glutathione (GSH) content in the liver of the rats administered with CCL 4 decreased significantly compared to that in all other treatment groups, whereas rats pretreated and co-administered with cod liver oil and CCl 4 showed significant (p<0.05) improvement in the liver GSH content. The catalase (CAT) activity in the liver of rats exposed to CCL 4 decreased (p<0.05) significantly, whereas the activity increased (p<0.05) significantly in the rats that were treated with cod liver oil compared to the CCl 4 only-treated group. The percentage inhibition of superoxide dismutase (SOD) increased (p<0.05) significantly in the liver of rats administered cod liver oil compared to the CCL 4 -treated rats and the control. Conclusions: Taken together, cod liver oil attenuates CCL 4 -induced toxicity and oxidative stress in the liver but not in the kidney of rats acutely exposed to CCL 4 .

Background: Studies have shown that the hyperglycemic state induced by intravenous glucagon or glucose infusion may lead to inhibition of gastric acid secretion through the inhibition of gastric vagus activity. Histamine is a well-known mammalian acid secretagogue and it stimulates acid secretion through H 2 receptors. Therefore, the aim of this study was to determine what effect an acute hyperglycemic or hypoglycemic state would have on histamine-stimulated acid secretion. Methods: Male Wistar rats weighing between 200 and 250 g were divided into three groups that received an intravenous infusion of normal saline (control group), glucose (hyperglycemic group), or insulin (hypoglycemic group) followed by injection of histamine to stimulate acid secretion. The oesophageal and duodenal ends of the rats’ stomach were cannulated with polythene tubing and the stomach was perfused at room temperature using a Langendoff perfusion apparatus. The effluent was collected in aliquots over 10 min per sample and its pH was measured. Results: There was a significant (p<0.05) decrease in acid secretion following histamine injection in the hyperglycemic rats, while histamine injection led to an increase (p<0.05) in acid secretion in the hypoglycemic rats. Conclusions: These results show that hyperglycemic state would result in attenuated histamine-stimulated gastric acid secretion, while hypoglycemic state would lead to increased histamine-stimulated gastric acid secretion.

Background: The present investigation was undertaken to evaluate the physiological characteristics of crab egg mass ( Portunus sanguinolentus ) crude extract. Methods: Assays were followed by standard methods. Results: A maximum of 256 hemolytic units (HU) and a minimum of 128 HU were found in chicken and goat erythrocytes. In an antimicrobial assay, Salmonella paratyphi and Aspergillus niger showed most susceptibility (8.0 mm and 13.0 mm) against n-butanol extracts. In the tail flick method, 5.33±0.19* AR the maximum analgesic response was recorded 30 min after the administration of crude extract (150 mg kg –1 ). In the hot plate method, 5.13±0.13* AR maximum paw licking was recorded 15 min after the administration of crude extract (150 mg kg –1 ). In an anti-inflammatory assay, 0.31±0.23* anti-inflammatory response and inhibition of paw edema 39.22% were observed 1 h after the administration of crude extract (250 mg kg –1 ). Primary structural groups gained through Fourier transformed infrared (FTIR) analysis peaks were observed and assigned as amide groups I (1517.81–1633.12 cm –1 ), II (1446.58–1517.81 cm –1 ) and III (1342.47–1406.85 cm –1 ). Conclusions: The results indicate that crab egg masses have remarkable antimicrobial, hemolytic and cytotoxic activities.

Background: The Cinnamomum zeylanicum (CZ; family Lauraceae) bark, an important spice, has also been used traditionally for nervous stress, as a nervine tonic, and as a stimulant. Therefore, the present study was designed to evaluate the effect of the standardized lyophilized aqueous extract of CZ bark (LCZE) on learning and memory in rodents at 50, 100, and 200 mg/kg, p.o. dose levels against streptozotocin (STZ)-induced memory impairment. Methods: LCZE was standardized based on the cinnamaldehyde content using high-performance thin-layer chromatography (HPTLC). The effect on learning and memory was evaluated using two widely used behavioral models, the Morris water maze (MWM) test and the object recognition test (ORT). The effect of LCZE on the acetylcholinesterase (AChE) activity and oxidative stress parameters in the cerebral cortex and hippocampus of rat brain was also evaluated. Results: LCZE significantly (p<0.05) and dose-dependently attenuated STZ-induced cognitive deficit in both models in comparison to only STZ-treated animals. In the MWM test, LCZE (100 and 200 mg/kg) significantly decreased the transfer latency and increased the time spent by the animals in target quadrant. Similarly in the ORT, the LCZE-treated animals exhibited an improved discrimination between a familiar object and a novel object, indicating the reversal of STZ-induced memory impairment. LCZE also restored STZ-induced alteration in AChE activity and oxidative stress parameters in both brain parts. Conclusions: The results clearly indicate toward the memory-enhancing effect of LCZE, which could be due to the synergistic effect of anti-AChE and antioxidant activities.

Background: The stem bark ethyl acetate extract of Erythrina lysistemon was found to induce vaginal proliferation in ovariectomized rats orally treated. Alpinumisoflavone (AIF) and abyssinone V-4′-methyl-ether (AME), isolated as its major constituents, were reported to separately provoke uterine growth and/or vaginal proliferation. The present study aimed at evaluating the effects of the mixture of AIF and AME (51 mg/kg [AIF]+153 mg/kg [AME]) following their relative abundance in the extract, in order to compare these effects to those of E. lysistemon . Methods: The study was performed in ovariectomized rats treated intraperitoneally for 3 days. Estradiol valerate (E 2 V) and AME were used for positive controls. Morphological and histological changes of animals’ uterus and vagina were used as the hallmark of estrogenicity. Results: E. lysistemon extract induced estrogen-like effects only on the uterus and significantly increased uterine wet weight (p<0.01) and uterine epithelial height (p<0.01). These results suggest a tissue-selective action of E. lysistemon extract depending on the route of administration. The mixture of AIF and AME induced E. lysistemon -like effects only at a dose of 1 mg/kg BW/d (0.25 mg/kg+0.75 mg/kg), although these effects were lower in magnitude (p<0.05) compared to those induced by E. lysistemon extract. Conclusions: Effects induced by the mixture of AIF and AME are analogous to those of E. lysistemon , but the low magnitude of these effects suggests that there are minor metabolites that interact with AIF and AME to provoke the specific effects of E. lysistemon .

Background: Hypertension is a chronic illness associated with high morbidity and mortality. Once hypertension is diagnosed, starting antihypertensive therapy on a long-term basis along with regular follow up is important. Standardizing treatment guidelines and conducting drug utilization studies at regular intervals help physicians to prescribe drugs rationally. The present study was conducted to analyze the prescription patterns of antihypertensive drugs in a tertiary care referral hospital in Malabar region, Kerala, India. Methods: The study was conducted at the General Medicine and Cardiology Department involving the in-patients. Patients suffering from essential hypertension with or without other co-morbidities were included in the study. The frequency and proportion of prescribing different groups of antihypertensive drugs as monotherapy or combination therapy, and prescription of fixed drug combinations (FDCs) were analyzed. A total of 200 hypertensive patients were included in the study. Patient data were collected from in-patient’s case sheets and direct interviews with the patients and their observers. Results : The majority of the patients were females with 56%, whereas the males comprised 44%, with most of the patients suffering from stage-II hypertension. The study revealed that a high proportion of the hypertensive patients had co-morbid diabetes mellitus. The most commonly prescribed class of antihypertensive drugs was angiotensin receptor blockers, followed by calcium channel blockers and β-blockers. With regard to patient therapy, 32.0% received monotherapy, whereas 68.0% received combination therapy, 16% of which received FDCs. Conclusions: The study shows that clinical pharmacists can play a key role in promoting rational prescription and improving adherence to medication.

Background: Adenia cissampeloides (Planch ex. Hook) Harms (Passifloraceae) leaf infusion is used in traditional African medicine as a stimulant to treat depression and insanity. Thus, this study investigates antidepressant and anxiolytic activities of the hydroethanol leaf extract of Adenia cissampeloides (ACE) in mice. Methods: ACE (50–200 mg/kg, p.o.) was administered to mice 1 h before behavioral studies; the forced swimming test (FST), tail suspension test (TST), elevated-plus maze test (EPM) hole-board test (HBT) and open field test (OFT). In addition, the probable mechanisms of antidepressant- and anxiolytic-like actions of ACE were also investigated. Results : ACE (100 and 200 mg/kg) produced significant (p<0.01) reduction in immobility, along with a significant increase in swimming activity (75.20%) and climbing (190.00%), respectively, similar to anti-immobility effect of imipramine in the FST. Also, in TST, ACE (100 and 200 mg/kg) treatment significantly (p<0.01) reduced the immobility time by 35.60%, and 35.27%, respectively, which was similar to anti-immobility effect of fluoxetine (32.50%). However, the antidepressant-like effect produced by ACE was prevented (p<0.01) by yohimbine (α 2 -adrenoceptor antagonist), or sulpiride (dopamine D 2 receptor antagonist) pretreatment. ACE (50 and 100 mg/kg) treatment (p<0.01) increased number (41.67%) and duration of head-dips (52.27%) in HBT. Similarly, ACE (50–200 mg/kg) increased duration of open arm entries (p<0.001) in EPM. However, this effect was reversed (p<0.001) by pretreatment of mice with cyproheptadine (5-HT 2 receptor antagonist) (60.87%). Conclusions : Findings from these studies revealed antidepressant-like effect of ACE mediated through interaction with dopamine D 2- receptor or α 2 -adrenoceptor. Also an anxiolytic-like effect through interaction with 5-HT 2 receptors.

Background: Recent studies in standard laboratories have indicated that a typical mango stem bark aqueous extract ( Magnifera indica Linn) possess anti-malaria and anti-fever properties. Recent information also exists in the literature, suggesting its potency as a very effective anti-inflammatory plant extract. This study will therefore contribute immensely to the systemic search for a useful, less toxic and natural bioactive medicinal compound. Objectives: This study investigated the anti-inflammatory effects of the aqueous extract of Mangifera indica (MI) in a carrageenin-induced rat paw oedema model of acute inflammation. Methods: Rats (n=5) were treated orally with MI (50, 100 and 200 mg/kg), acetylsalicylic acid (100 mg/kg) or distilled water (3 mL). Thirty minutes later, acute inflammation was induced with a sub-plantar injection of 0.1 mL of 1% carrageenin solution into the right hind paw of the rats. The paw oedema sizes were measured with the aid of a Vernier calliper over a period of 3 hours. Results: The aqueous extract of MI (50–200 mg/kg, p.o.) produced a dose-dependent and significant inhibition of the acute inflammation induced by the carrageenin in rats when compared with controls. The percentage inhibition of oedema formation produced by MI (200 mg/kg, p.o.) was similar to that elicited by acetylsalicylic acid (100 mg/kg, p.o.). Conclusions: The results of this preliminary investigation suggest that MI contains active compounds with an anti-inflammatory activity. However, more detailed studies using additional models are necessary to further characterise the effects of MI in inflammatory disorders.