Effects of Clarithromycin Administration on Gastric Acid Secretion and Cytoprotection in Wistar Rats.

The incidence of peptic ulcer disease in Nigeria is 28% (Ndububa and Adeyemi, 2008). Clarithromycin (CLX) is used in the treatment of peptic ulcer owing to its antibacterial effect. Whether CLX has effects on other gastrointestinal parameters that reduce peptic ulcer has not been previously investigated. Therefore the effects of CLX on gastric acid secretion, mucus secretion and gastric ulcer scores in rats were investigated. A total of 30 albino wistar rats were used for the study. Out of this number, 10 rats each were used for gastric acid secretion, mucus secretion and ulcer scores respectively. In each of these sub groups, 5 rats served as test and were treated with CLX orally and 5 rats served as control. Standard methods were used for the estimation of these parameters of gastric function. The results showed that basal gastric acid, peak acid output following histamine stimulation and mucus secretion were significantly increased (p<0.001) in CLX-treated (test) rats than in their control. Furthermore, ulcer scores were significantly reduced (p<0.001) in the CLX-treated rats than control. In conclusion, Clarithromycin administration reduced gastric ulcers in rats. This may be attributable to not only its antibiotic property but also its ability to increase gastric mucus which counteracts the aggressive effect of the acid.

Haemostatic Indices as Markers for Monitoring Pulmonary Tuberculosis Treatment.

Tuberculosis (TB) is an infectious disease inducing a state of chronic inflammation which could affect thehaemostatic mechanism as part of host defences against infection. Proper diagnosis and monitoring of tuberculosis patientsundergoing therapy is still a challenge especially in a poor resource country such as Nigeria. This study aims to assess somehaemostatic indices of tuberculosis patients and their possible use as markers in monitoring response to anti-tuberculosistreatment. One hundred and twenty TB patients aged 15-60 years and 120 apparently healthy (control) subjects age andgender-matched were studied. Demographic/bio data was compiled by interview and from patients' case notes. Diagnosis ofTB was by sputum smear microscopy, radiography and clinical assessment. Platelet count (PLT), platelet factor 4 (PF4),prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin clotting time (TCT) and fibrinogen (FIB)were determined using standard techniques. The platelet factor 4, prothrombin time, activated partial thromboplastin timeand fibrinogen levels of TB patients were significantly higher while the thrombin clotting time was significantly lower(P<0.05) when compared with healthy subjects. While PF4, TCT and FIB improved significantly (P<0.05) as antituberculosis therapy progressed, PLT, PT and APTT remained the same. It is concluded that abnormal activation ofhaemostasis occurs in TB condition thus pre-disposing TB patients to bleeding complications. Furthermore, platelet factor4, thrombin clotting time and fibrinogen improved as therapy progressed and therefore may be used as markers for monitoringresponse to anti-tuberculosis therapy.

Altered Potassium Ion Channel Function as a Possible Mechanism of Increased Blood Pressure in Rats Fed Thermally Oxidized Palm Oil Diets.

Intake of thermally oxidized palm oil leads to cytotoxicity and alteration of the potassium ion channel function. This study investigated the effects of fresh and thermally oxidized palm oil diets on blood pressure and potassium ion channel function in blood pressure regulation. Male Wistar rats were randomly divided into three groups of eight rats. Control group received normal feed; fresh palm oil (FPO) and thermally oxidized palm oil (TPO) groups were fed a diet mixed with 15% (weight/weight) fresh palm oil and five times heated palm oil, respectively, for 16 weeks. Blood pressure was measured; blood samples, hearts, and aortas were collected for biochemical and histological analyses. Thermally oxidized palm oil significantly elevated basal mean arterial pressure (MAP). Glibenclamide (10-5 mmol/L) and tetraethylammonium (TEA; 10-3 mmol/L) significantly raised blood pressure in TPO compared with FPO and control groups. Levcromakalim (10-6 mmol/L) significantly (p < .01) reduced MAP by 32.0% in FPO and by 5.4% in TPO. NS1619 (10 mmol/L) significantly (p < .01) decreased MAP by 19.5% in FPO and by 8% in TPO. The TPO significantly (p < 0.01) increased the tissue levels of peroxide, total cholesterol, triglyceride, and low-density lipoprotein cholesterol while catalase and superoxide dismutase activities were significantly (p < .01) decreased compared with control and FPO groups. Histological alterations were prominent in aortas and hearts of rats in the TPO group. These results suggest that prolonged consumption of repeatedly heated palm oil increases MAP probably due to the attenuation of adenosine triphosphate-sensitive potassium (KATP) and large-conductance calcium-dependent potassium (BKCa) channels, tissue peroxidation, and altered histological structures of the heart and blood vessels.

Cadmium chloride-induced testicular toxicity in male wistar rats; prophylactic effect of quercetin, and assessment of testicular recovery following cadmium chloride withdrawal.

This study assessed the effect of quercetin (QE) on cadmium chloride (CdCl2) - induced testicular toxicity, as well as the effect of withdrawal of CdCl2 treatment on same. Thirty male Wistar rats aged 10 weeks old and weighing 270-300g were assigned into 5 groups and used for this study. Rats in groups 1-4 were administered vehicle, CdCl2 (5mg/kg bwt), CdCl2+QE (5mg/kg bwt and 20mg/kg bwt, respectively) or QE (20mg/kg bwt) orally for 4 weeks. Group 5 rats received CdCl2, with 4 weeks recovery period. Results showed that cadmium accumulated in serum, testis and epididymis, decreased body weight, testicular and epididymal weights, sperm count, motility and viability. Cadmium decreased serum concentrations of reproductive hormones, but increased testicular glucose, lactate and lactate dehydrogenase activity. Cadmium decreased testicular enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic (glutathione, vitamins C and E) antioxidants, and increased malondialdehyde and hydrogen peroxide. Cadmium down-regulated Bcl-2 protein, up-regulated Bax protein, increased Bax/Bcl-2 ratio and cleaved caspase-3 activity. Histopathology of the testis showed decreased Johnsen's score and Leydig cell count. These negative effects were attenuated by QE administration, while withdrawal of CdCl2 did not appreciably reverse toxicity. We conclude that QE better protected the testis from CdCl2 toxicity than withdrawal of CdCl2 administration.

Chronic consumption of three forms of palm oil diets alters glomerular filtration rate and renal plasma flow.

The effects of chronic consumption of three types of palm oil diets on glomerular filtration rate (GFR), renal plasma flow (RPF) and blood pressure were studied. Wistar rats were randomly assigned into four groups of ten rats each, respectively: control, fresh (FPO), photoxidized (PPO), thermoxidized (TPO) palm oil diet-fed rats. The control group was fed rat chow only, while experimental groups had different palm oil diets at 15% wt/wt for twelve weeks and tap water ad libitum. After the feeding period, GFR, RPF, systolic and diastolic blood pressures were measured. GFR and RPF of the TPO (0.07 ± 0.01 ml/min and 1.50 ± 0.24 ml/min) and PPO (0.14 ± 0.01 and 2.54 ± 0.11) groups were significantly (p < 0.001) reduced compared with control (0.77 ± 0.04 and 5.3 ± 0.30) and FPO (0.81 ± 0.02 and 4.8 ± 0.13) groups. The GFR and RPF of the TPO group was significantly (p < 0.05) higher than that of the PPO group. Systolic and diastolic blood pressures of the TPO group (140 ± 3 mmHg and 106 ± 4 mmHg) were significantly (p < 0.01) increased when compared with the control (112 ± 6.4 and 78 ± 5), FPO (118 ± 5 and 81 ± 6) and PPO (122 ± 5 and 89 ± 5) groups. These results suggest that chronic consumption of TPO and PPO caused a decrease in GFR and RPF, but increased blood pressure in rats, while FPO did not adversely affect blood pressure, GFR and RPF.

Attenuated vascular responsiveness to K+ channel openers in diabetes mellitus: the differential role of reactive oxygen species.

The current study examined the responsiveness of blood vessels from diabetic rats to K+ channel openers and explored whether ROS might be involved in any changes. Responses were measured in aortic rings isolated from four weeks streptozotocin (65 mg/kg)-induced diabetic rats. Relaxation to levcromakalim (ATP-sensitive potassium channel KATP opener, 10(-9)-10(-5) mol/l) and (+/-)-naringenin (large conductance calcium-activated channel BKCa opener, 10(-8)-10(-3) mol/l) were recorded in phenylephrine (1 µmol/l) pre-contracted segments in the absence and presence of superoxide dismutase (SOD, 100 µmol/l) and apocynin (an antioxidant and inhibitor of NADPH oxidase, 100 µmol/l). Contractions to phenylephrine (10(-9)-10(-5) mol/l) and relaxation to acetylcholine (ACh, 10(-9)-10(-5) mol/l) were also recorded. Relaxation curves for levcromakalim, naringenin and ACh for the diabetic group were shifted to the right (p < 0.05) compared with the control. Contractions to phenylephrine were enhanced in the diabetic group (p < 0.01). SOD restored the ACh response but not those of K+ channel openers. On the other hand, apocynin restored the relaxation to naringenin but had no effect on both levcromakalim and ACh responses. The results suggest that both KATP and BKCa activities are attenuated in diabetes mellitus and that ROS appears to contribute only to the change in BKCa function.

Gastric ulceration in diabetes mellitus: protective role of vitamin C.

The effect of vitamin C administration on gastric acid secretion and ulcer in diabetic rats was studied. Vitamin C (200 mg/kg b.w.) was administered to both streptozotocin-induced diabetic and control groups orally for 28 days. Gastric acid secretion was measured and ulcer was induced using ethanol. Histological changes were observed in the stomach. Basal and stimulated acid secretion in diabetic control rat was significantly (P < 0.01) decreased when compared to vitamin C-treated diabetic group and control. Administration of vitamin C significantly (P < 0.05) increased the histamine-stimulated gastric acid secretion in diabetics than control while reduction in gastric secretion by ranitidine was similar compared with control. Vitamin C treatment significantly (P < 0.05) reduced ulcer index in diabetic group and increased mucus weight when compared with diabetic group which was also confirmed with photomicrographs. The mean body weight of diabetic rats treated with vitamin C was comparable to the control. The blood glucose level was significantly (P < 0.01) reduced in diabetic group given vitamin C (8.9 ± 1.8 mMol/L) compared to the diabetic control (32.2 ± 2.1 g). It is concluded that vitamin C is beneficial in improving gastric acid secretion and protects against ulceration in streptozotocin-induced diabetes mellitus in rats due to its antioxidant potential.

Intestinal Fluid and Glucose Transport in Wistar Rats following Chronic Consumption of Fresh or Oxidised Palm Oil Diet.

Chronic ingestion of thermoxidized palm oil causes functional derangement of various tissues. This study was therefore carried out to determine the effect of chronic ingestion of thermoxidized and fresh palm oil diets on intestinal fluid and glucose absorption in rats using the everted sac technique. Thirty Wistar rats were divided into three groups of 10 rats per group. The first group was the control and was fed on normal rat chow while the second (FPO) and third groups (TPO) were fed diet containing either fresh or thermoxidized palm oil (15% wt/wt) for 14 weeks. Villus height and crypt depth were measured. The gut fluid uptake and gut glucose uptake were significantly (P < .001) lower in the TPO group than those in the FPO and control groups, respectively. The villus height in the TPO was significantly (P < .01) lower than that in FPO and control. The villus depth in TPO was significantly (P < .05) higher than that in FPO and control groups, respectively. These results suggest that ingestion of thermoxidized palm oil and not fresh palm oil may lead to distortion in villus morphology with a concomitant malabsorption of fluid and glucose in rats due to its harmful free radicals.