Experimental benefits of telmisartan, avandamet and some natural plant extracts on glucose metabolism and insulin secretion in fructose-fed rats

Non-insulin dependent diabetes mellitus [NIDDM] is often associated with hypertension leading to specifically high cardiovascular risk in these patients. However, there is evidence that insulin resistance and hyperinsulinemia are not only characteristic for diabetic patients but also for some non-diabetic populations in whom a cluster of cardiovascular risk factors is observed [hypertension, hypentriglyceridemia, obesity]. Therefore, hyperinsulinemia and IR have been suggested to be of major pathophysiological importance for the development of this syndrome [syndrome X]. Hence, the aim of this study was to evaluate the influence of avandamet [Av] as an example of anti-diabetic drug, telmisartan [Tel] as a anti-hypertensive agent and some plant extracts such as Paranica egyptica [Para] and holy basil leaves [Holy] on glucose tolerance in vivo. Male Wistar rats were recruited and divided into six groups [6 rats/group]. Rats were randomly assigned into six groups, each consisted of six animals. Each rat was weighed and its blood pressure taken at the start of the study using the rat tail method. In addition, sampling of the orbital sinus was done and the blood glucose level was measured using a glucometer. The first group of rats was allowed to grow on chow diet and served as normal controls. The remaining rats were fed high fructose diet for 5 weeks for induction of insulin resistance model according to Rosen et al. These rats were then divided into five groups: the first group of fructose-fed rats was left without treatment [Fr-f group]. Telmisartan was given orally to the 2[nd] group of fructose -fed rats once daily at a dose of 3.6 mg kg[-1] for 2 weeks [Fr-f + Tel group]. Avandamet was administered orally to the 3rd fructose-fed group once daily at a dose of 0.4 mg kg[-1] for a period of 2 weeks [Fr-f+ Av group]. The remaining fructose-fed animals were given either the aqueous extract of Paranica egyptica at a daily oral dose of 3.6 ml kg[-1] for 2 weeks [Fr-f+ Para group] or the aqueous extract of holy basil leaves in a similar dose regimen as described above [Fr-f+ Holy group]. At the end of the experiment the body weight [BW], blood pressure [BP1] and blood glucose [BIG] were measured. Afterwards, the animals were killed and serum was used for the measurement of insulin. The results from the present study showed an increase in body wt, blood pressure, blood glucose, serum insulin and insulin resistance in the fructose-fed group versus the control, Para, Holy, Av, and Tel, groups, respectively. Although treatment with para, holy on avandamet significantly reduced the observed increases in all the studied parameters in comparison to the fructose-fed groups, they still were higher than the control group. In conclusion, fructose administration resulted in increased body weight, blood pressure, blood glucose, serum insulin, and insulin resistance [with respect to their control groups]. Avandamet [rosiglitazone + metformin], in addition to the herbal natural extracts, Paranica and holy basil appear to be beneficial in controlling glucose homeostasis and insulin secretion in type 2 experimental diabetes with insulin resistance. So, the use of these naturally-occurring agents, in conjunction with conventional drug therapies may permit the use of lower doses and/or decrease their commonly observed side effects. Further studies are essential to elucidate the exact mechanism of actions of these herbal agents, and examine their potential therapeutic effects

Apoptosis and endotoxins-induced secretion of interleukin-1B and tumor necrosis factor O by mononuclear cells in patients with acute versus chronic renal failure

Previous reports suggested a protective effect of chronic renal failure [CRF] against sepsis and endotoxin-induced organ failure and mortality in ARF. The present study was undertaken to investigate apoptosis and endotoxin-induced total production and secretion of interleukin-IB [IL-1B] and secretion of tumor necrosis factor a [TNF alpha] by mononuclear cells in patients with acute versus chronic renal failure. Lipopolysaccharide [LPS] induced IL-1B total production and secretion and TNF alpha secretion by peripheral blood mononuclear cells [PBMC] cultured for 18 hours were determined in patients with advanced CRF but not yet on dialysis [n=13], ARF patients [n=10] and healthy controls [n=10]. In vitro spontaneous apoptosis of cultured PBMC [for 18 hours] was also determined in these subjects. Suppressed secretion of IL-1B [629 +/- 490 pg/ml] by LPS stimulated PBMS was found in patients with CRF compared to patients with ARF [1989 +/- 1209 pg/ml, P<0.05] and healthy controls [1543 +/- 107.3 pg/ml, P<0.05]. A decrease in the total [1346 +/- 998.6 pg/ml] and cell associated [717 +/- 534 pg/ml] LPS induced IL-IB production was also found in them compared to those with ARF [39005 +/- 2516 pg/ml, P<0.05 and 1917 +/- 1308 pg/ml, P<0.05 for total and cell associated levels respectively]. Total production and secretion [absolute value] of LPS induced IL-1B were similar in patients with ARF and healthy controls but with increased cell associated IL-1B production in patients with ARF [P<0.05] LPS-induced TNF alpha secretion by PBMC did not differ significantly in the three groups. Accelerated spontaneous apoptosis of PBMC was found in patients with CRF [30.6 +/- 6.2%] compared to healthy controls [15.8 +/- 9.9%, P<0.05] and to patients with ARF [16.4 +/- 4.7%, P<0.05]. Negative correlation was found between% apoptosis of PBMC and secretion of both LPS induced IL-1B [P<0.01] and TNF alpha [P<0.01] by PBMC in patients with CRF. The reduced capability of PBMC from patients with CRF to secrete adequate amounts of IL-1B in response to LPS together with the accelerated spontaneous apoptosis may be protective mechanisms that decrease the deleterious effect of tissue necrosis and may partly explain the reported fair prognosis of ARF and sepsis in cases with prior CRF