Two separate studies were performed on hypertensive rats to assess the effects of wild, uncultivated garlic on elevated systolic blood pressure (SBP) and other cardiovascular parameters. Also, effects of wild garlic and cultivated garlic preparations were compared and the mechanisms behind pressure-lowering abilities of different garlic preparations were examined. The initial study determined that wild garlic lowers blood pressure. In the second study, cardiovascular effects of three different concentrations of wild garlic and two different cultivated garlics, i.e., a preparation low in allicin and one high in allicin, were compared. All three garlic preparations decreased SBP significantly. Wild garlic produced the greatest pressure-lowering effects, and the least pressure-lowering effects were seen with low-allicin garlic. Compared with control rats, circulating angiotensin II levels were significantly lower in all garlic-eating rats. Losartan decreased blood pressure significantly less and Nw-nitro-L arginine-methyl ester hydrochloride (LNAME) increased blood pressure significantly more in garlic-eating rats than in control rats, suggesting that the renin-angiotensin system (RAS) was less active and the nitric oxide system more active in garlic-consuming hypertensive rats. Accordingly, different garlic preparations, especially wild garlic, favorably influenced high SBP in hypertensive rats. These results suggest that both the RAS and the nitric oxide system are involved in the antihypertensive effects of garlic in hypertensive rats.

Animals↗

PubMedDate not supplied

Acute and long-term safety evaluation of a novel IH636 grape seed proanthocyanidin extract.

Grape seed proanthocyanidins are known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties. Previous studies in our laboratories have demonstrated the various protective abilities of a novel IH636 grape seed proanthocyanidin extract (GSPE) against various pathologic conditions. However no extensive safety studies have been conducted on grape seed proanthocyanidins to date. This study demonstrates the acute and chronic safety studies on GSPE. Acute oral toxicity, dermal toxicity, dermal irritation and eye irritation studies have been conducted. The LD50 of GSPE was found to be greater than 5000 mg/kg when administered once orally via gastric intubation to fasted male and female albino rats. The LD50 of GSPE was found to be greater than 2000 mg/kg when administered once for 24 hr to the clipped, intact skin of male and female albino rats. In addition, 2000 mg/kg was found to be the no-observed-effect level (NOEL) for systemic toxicity under the conditions of the study. In a dermal irritation study, GSPE received a descriptive rating classification of moderately irritating. Extensive chronic studies were also conducted. We have assessed the effects of chronic administration of 100 mg GSPE/kg/day for twelve months and its effect on seven vital target organs, namely, brain, heart, intestine, kidney, liver, lung and spleen, and on serum chemistry changes in male B6C3F1 mice. Furthermore, the dose-dependent chronic effects of GSPE in female B6C3F1 mice were evaluated. Mice were fed 0, 100, 250 or 500 mg GSPE/kg/day for six months and the effects of GSPE exposure were examined on brain, duodenum, heart, kidney, liver, lung, pancreas and spleen, and on serum chemistry changes in female mice. These acute studies demonstrated that GSPE is safe and did not cause any detrimental effects in vivo under the conditions investigated in this study.

Administration, Topical↗

PubMedDate not supplied

Hepatoprotective ability of a novel botanical formulation on mild liver injury in rats produced by acute acetaminophen and/or alcohol ingestion.

Medicinal herbs have been used for centuries in an attempt to overcome hepatic dysfunctions emanating from ingestion of hepatotoxic substances. However, the vast majority of information concerning their use is anecdotal. Well-performed animal studies would lend credence to the concept that some medicinal herbs may prevent or, at least ameliorate, hepatic dysfunction arising from drug-induced toxicity. The present investigation examined the potential for a combination of medicinal herbs to favorably influence the course of mild/moderate acute hepatic injury induced in rats by the oral intake of acetaminophen and/or ethyl alcohol. We performed four separate studies using elevations of liver enzymes [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] as our primary biomarkers of hepatotoxicity. In the first study, the ability of orally administered acetaminophen at different doses to produce acute hepatotoxicity was examined. In the second and third studies, the ability of a combination of medicinal herbs (a novel botanical formulation) was assessed to ameliorate the acetaminophen-induced hepatotoxicity. In the last series of studies, we used acute alcohol ingestion to cause liver perturbations and examined the ability of medicinal herbs to overcome hepatotoxicity. We also evaluated the ability of the medicinal herb combination to overcome acetaminophen-induced hepatotoxicity in rats simultaneously challenged with ethyl alcohol ingestion. Hepatotoxicity, estimated by increased levels of AST and ALT, was produced by a 2.0 mg/Kg oral dose of acetaminophen but not by lesser doses. Treatment with a combination of medicinal herbs (a novel botanical formulation) significantly ameliorated acetaminophen-induced toxic response. The combination of medicinal herbs also decreased the hepatic toxicity produced by acute ethyl alcohol ingestion. We conclude that oral ingestion of a novel botanical formulation (a combination of medicinal herbs) is effective in lessening drug-induced hepatotoxicity produced by acetaminophen and/or ethyl alcohol in an animal model.

Acetaminophen↗

PubMedDate not supplied

Early sucrose-induced retinal vascular lesions in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY).

Retinal capillary basement membrane damage was demonstrated over a relatively short time period (two to three months) by feeding a diet containing high amounts of sucrose to spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto rats (WKY). Similar changes did not occur in SHR and WKY on a high starch diet. The early damage to the capillaries consisted of thickening of capillary basement membranes, loss of homogeneity, and inclusions containing debris. Previous studies on sucrose-induced eye lesions have reported chronic pathological changes only after prolonged periods of heavy sucrose ingestion, usually exceeding one year. Accordingly, the temporally foreshortened experimental pathogenesis offered by the SHR/WKY model allowed us to examine early changes in sucrose-induced vascular eye lesions.

Animals↗

PubMedDate not supplied

Further studies on a renotropic system in rats.

Based upon many investigations, the existence of short-lived, specific, circulating substances which incite and/or regulate compensatory renal growth has been proposed. In our studies, we find that sera and plasma from unilaterally nephrectomized rats compared to sera and plasma from sham-operated rats stimulate the incorporation of (3)H-thymidine monophosphate, (3)H-thymidine and (14)C-uridine into the DNA of incubating rat kidney fragments. While extracts from growing rat kidneys are not excitatory, they produce a relative enhancement to incorporation of isotope into DNA when combined with sera from uninephrectomized rats-more than the sera do alone. The above is found also for the incorporation of (14)C-uridine into RNA of incubating rat kidney fragments. Sera from uninephrectomized rats fail to stimulate DNA synthesis in liver slices from rats but do so in the presence of extracts from growing kidneys. Renotropic factors in sera and extracts do not appear to work by diluting the isotopes, by enhancing transport, or by effecting overall metabolism of the renal cells. The above described serum and liver factors may play a role in compensatory renal growth.

Animals↗