Effect of quercetin on brain protein kinase C-alpha expression and serotonin level in streptozotocin-induced diabetic rats

Hyperglycemia is a key factor in diabetic complications. However, the mechanism of hyperglycemia-induced brain changes remains poorly understood. The aim of the present study was to investigate the effect of diabetes on serotonin [5-hydroxytryptamine; 5-HT] levels and protein kinase C-alpha [PKC-alpha] expression in brain. The potential protective effect of quercetin [QE]; as phytochemical on diabetic brain was additionally studied. This study was carried out on 60 adult male albino rats divided into three main groups; group I [control] included 20 vehicle-treated rats, group II [diabetic] consisted of 20 rats injected once intraperitonially with streptozotocin [STZ; 50mg/kb body weight] amid group III [insulin-treated diabetic] comprised 20 diabetic rats injected subcutaneously with insulin [SIU/kg/day]. Each group was subdivided into 2 subgroups; subgroup I [non-QE treated] and subgroup 2[QE-treated]. QE was administered orally [10mg/kg/day]. At the end of the implemental period, all rats were sacrificed, blood samples were withdrawn and their brains were rapidly removed and dissected. 5-HT was extracted from brain samlples and their concentrations were estimated fluorophotometrically. PKC-alpha expression was quantitated by immunoblot from extracted brain samples. The STZ-induced diabetic rats showed significant marked hyperglycemia and higher brain PKC-alpha expression as compared to both control and insulin-treated diabetic groups. However, brain 5-HT concentrations did not differ significantly between the three studied groups. Only in diabetic rats, QE administration produced a significant increase in 5-HT concentrations and a decrease in PKC-alpha expression but with no effect on blood glucose levels. A highly significant direct correlation was found between blood glucose and PKC-alpha expression levels. However, 5-HT did not correlate with either blood glucose or PKC-alpha expression. it could be concluded that STZ-induced chronically hyperglycemic rats were associated with enhanced PKC-alpha expression as well as unaltered neurotransmitter; 5-HT in brain. QE seems to act perfectly in diabetic rats by mechanisms other than antihyperglycemic action. The neuroprotective effect of QE in diabetics was suggested to be through both elevating 5-HT and lowering PKC-alpha expression. Consequently, controlling hyperglycemia is still the most essential approach for primary prevention of diabetic complications

Study of endothelin in portal hypertension

The aim of this study was to evaluate the plasma level of endothelin -1 in portal hypertension in patients with hepatic cirrhosis. Thirty patients with portal hypertension due to cirrhotic liver were studied at the Critical Care Medicine and Internal Medicine departments at Alexandria Main University Hospital. Clinical evaluation of the severity of illness was done using Modified Child- Pugh Score and portal hypertension was assessed by doing Duplex Doppler ultrasonogram. Plasma levels of endothelin-1 [ET-1] were estimated by radioimmunoassay. Plasma levels of endothelin-1 [ET-1] were significantly higher in patients with portal hypertension than control group [mean +/- SD was 94.3 +/- 14.91, 33.8 +/- 5.39 ng/ml respectively, p=.000]. Also, the study showed that plasma levels of ET-1 were significantly higher in patients with ascites than without [mean +/- SD was 104.15 +/- 11.71, 86.77 +/- 12.68 ng/ml respectively, p= .001]. The levels of ET-1 were significantly higher with the increased severity of liver disease according to modified Child -Pugh score [F = 10.25, p = .005]. Plasma ET-1 concentrations were increased in patients with portal hypertension with or without ascites, compared with controls. Patients with cirrhosis and ascites have increased ET-1 concentrations compared with those without ascites. The degree of increasing of plasma levels of endothelin was related to the severity of liver disease. The result of the present work may be of help in understanding the mechanism and may open a new field in the management of portal hypertension

Assessment of the anti-inflammatory action of some drugs

The aim of the present work was a study of the acute toxicity, the anti-inflammatory activity as the analgesic potency of salicylates, oxyphenbutazone, hydrocortisone and propranolol The L.D[50] was found to be 300 mg/kg., 460 mg/kg., 750 mg/kg. and 36 mg/kg respectively. All tested drugs induced a significant anti-inflammatory activity sod. Salicylate was the most potent, while propranolol was the least effective one. Sod. salicylate, hydrocortisone and oxyphenbutazone exerted a significant analgesic activity following the hot plate method, but by using the tail compression test only sod. salicylate exerted analgesic activity

Correlation of the rise in serum acid phosphatase with the degree of hyperglycaemia and vasculopathy in diabetic patients

Serum acid phosphatase and oral glucose tolerance test [OGTT] have been determined in thirty one diabetic patients [thirteen males and eighteen females], and ten normal subjects [five males and five females]. In male patients, the prostatic fraction of the enzyme has also been determined, in addition to the total enzyme activity. In the diabetic patients there is a significant increase in serum acid phosphatase. In male patients the increase was due to rise of the non prostatic fraction of the enzyme. The diabetics were classified into four groups according to the fasting blood glucose level: the first having a fasting level below 100 mg%, the second from 100-200 mg%, the third from 200-300 mg% and the fourth above 300 mg%. no positive correlation were found between the rise in serum acid phosphatase and the extent of impairment in glucose tolerance. Further classification of the diabetic patients was done according to presence or absence of diabetic vasculopathy. Serum acid phosphatase was significantly elevated in patients with vasculopathy, but in the other group without vasculopathy the enzyme level was not different from the normal control. It was concluded that the principle factor underlying rise of the serum acid phosphatase in diabetic patients is the presence of vasculopathy rather than the severity of glucose intolerance

Comparative toxicological study of some antibilharzial drugs

The data obtained in this work could be summarized as follows: 1. The LD 50 of tartar emetic was 49/kg, it produced a significant reduction of haemoglobin content and haematocrite value. It was the most toxic drug to the heart and lungs. Pharmacological studies showed that it produced direct depression on the isolated rabbits, heart, a perasympathomimetic effect manifested on isolated rabbits, intestine and blood pressure of anaesthetized dogs. 2. The LD 50 of astiban was 290 mg/kg. The results of subacute toxicity tests were similar to those obtained with tartar emetic but it was devoid of any toxic effect on heart. Pharmacological studies showed that it produced parasyupathomimetic effect on isolated rabbit's heart. 3. LD 50 of Hycanthone was 57 mg/ kg. No effect on the blood picture of rats was observed it was more toxic to the liver. It produced direct cardiac inhibition on the isolated rabbit's hearts, parasympathomimetic effect on the isolated rabbit's intestine and blood pressure of dog. 4. LD 50 of niridazole was 990 mg/ kg. The results of subacute toxicity tests were similar to those obtained with hycanthone. It is more toxic to brain it produced direct cardiac inhibition on the rabbit's heart and hypotension in dog