Toxicity assessment of watermelon seed supplemented diet in rats.

Health benefits have been attributed to the consumption of watermelon (Citrullus lanatus L.) seeds in sub-Saharan Africa and Asia but the potential toxicity especially on chronic use remains to be investigated. Here, diets containing watermelon seeds (WMSs) at 2.5% or 5% were eaten ad libitum daily for 21 d by male and female Wistar rats. Changes in body and organ (liver, kidney, brain, testis, and ovary) weights following diet supplementation were monitored. Biomarkers of organ injury, such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), cholesterol (CHO), triglyceride (TRI), urea, and creatinine (CRE) were measured. WMS-formulated diet led to a decrease in body weight in male but not in female rats compared to the control group. Also, testes weight significantly increased, whereas a decrease in that of the ovaries was noted. Although the ingestion of WMS did not significantly alter the weights of the liver and brain, a trend toward reduction was noticed. No significant changes were observed for the serum levels of ALT, ALP, CHO, and TRI in all rats. However, the kidney may be targeted for toxicity as indicated by significant elevations in serum urea and CRE levels in male and female rats when compared to controls. Furthermore, the sperm morphology anomalies observed after WMS supplementation demonstrate the potentially detrimental effects of high consumption of the seeds on the male reproductive system. We conclude that WMSs at 2.5% or 5% dose in the diet may elicit negative effects in organs particularly on the kidney and testes in rats.

Analgesic, anti-inflammatory and toxic effects of ethanol extracts of Cucumis melo and Citrullus lanatus seeds.

Plants are vital in drug discovery, since many safe and bioactive molecules have been discovered from plants in past, hence this study was designed to evaluate analgesic, anti-inflammatory and toxic effects of Cucumis melo and Citrullus lanatus. Seeds of these plants were selected due to their traditional value for medicinal use. Analgesic activity was determined in mice by Eddy's Hot plate and tail flick method, while anti-inflammatory activity was evaluated by hind paw edema method. Both seed extracts produced highly significant analgesic effects comparable to standard drugs at all three doses by both methods. The extract of C. lanatus showed significant anti-inflammatory activity at 100 mg while showed highly significant activity at 200 mg between 3 to 24 hours as compared to standard drugs. Both extracts did not reveal any mortality up to 1000mg/kg, while there was also no change in normal the gross behavior pattern of the animals at the dose of 50 and 100mg/kg, however there was increase in passivity, sedation and startle response at 200mg/kg. Analgesic and anti-inflammatory effects of extracts may be due to presence of cucurbitacin A, B or E in both seeds which are thought to inhibit COX 2. Results indicate that seeds of C. melo and C. lanatus may be effectively used as adjuvant analgesic and anti-inflammatory agents in situation of chronic pain and inflammation.

[Pharmaco-toxicological and clinical studies with colocynth pulp extracts (Extr. colocynthidis fructus)]. / Pharmakologisch-toxikologische und klinische Untersuchungen mit Koloquinthenfruchtextrakten (Extr. colocynthidis fructus).

Colocynth pulp extract is a long-serving laxative. Contesting the official characterizations "drastic irritant action, no longer defensible" by suitable pharmacotoxicologic studies, extracts of the drug with increasing concentrations of the effective constituant "Cucurbitacins" were prepared in order to define efficacy ranges lethal to rats and mice. The extract Koloquinthentrockenextrakt Alpha with the highest content of Cucurbitacins (23,2 % delta 232,64 mg/g) permitted the definition of the LD50 for female (tentative because of death inhibition under maximal doses) and male rats; the mean LD50 = 281,8 and 525,6 mg/kg extract, respectively, equivalent to 66 and 122 mg/kg Cucurbitacins. This corresponds to 660- to 1220-fold therapeutic doses. Repeated administrations of 10- and 50-fold therapeutic doses to rats for 30 days produced no negative effects. The symptoms of rodent poisoning are described in detail. Pharmacologic doses were not toxic on rat liver slices, did not influence breathing and circulation parameters in guinea pigs (under the maximal dose of 41,6 mg/kg Cucurbitacins, 3/10 animals died of breathing failure) nor the behaviour of mice, nor were they mutagen (Ames test). Colocynth pulp extract weakly inhibited the growth of MDA-MB435 mamma carcinoma cells, but had no influence on the growth of B16 mouse melanoma cells. P388 mouse leukemia cells and L 929 mouse fibroblasts were not significantly influenced. High doses of Colocynth pulp extract inhibited diuresis and electrolyte excretion in rats. The Cucurbitacins E and I were rapidly metabolized in S9-supernatants of rat livers. A dried ethanolic Salvia fruit extract alleviated the toxicity of lethal doses of Colocynth pulp extract when administered simultaneously. A field study with 200 patients and a phase I study with 60 volunteers were conducted in Germany with Colocynth pulp extract from April to October 1998, andfrom December 2002 to March 2003, respectively. Data on the tolerance of the highest allowed dose and of a half-maximal dose administered to volunteers for 14 days in comparison to placebo, as well as data on the efficacy of a treatment course of 3 days of patients with obstipation, were to be gained. Clinical laboratory investigations of volunteers gave no indication of pathological changes even under the highest dose. In patients with obstipation and associated complaints, the administration for 3 days at maximum led to an increased frequency of bowel movements. At the same time, the discomforts accompanying obstipation were significantly relieved. Patients with obstipation defined tolerance as good. Volunteers, on the other hand, judged the tolerance of the drug significantly inferior ("good" - "average") to that of placebo ("very good" - "good"). The low risk potential of Colocynth pulp extract documented in pharmaco-toxicological studies was confirmed during administration to humans.

Effect of combination of Capsicum frutescens and Citrullus colocynthis on growth, haematological and pathophysiological parameters of rats.

The toxicity of diet containing 10% of Capsicum frutescens or 10% of Citrullus colocynthis fruits or their 1:1 mixture (5% + 5%) to rats treated for 6 weeks was evaluated. Body weight loss, inefficiency of feed utilization, diarrhoea, and enterohepatonephropathy characterized C. colocynthis toxicosis in rats. Despite impairment of rat's growth neither nephropathy nor diarrhoea was detected in rats fed the 10% C. frutescens diet. Feeding the mixture of C. frutescens and C. colocynthis caused more pronounced effects and death of rats. Vital organ lesions accompanied by anaemia and leucopenia were correlated with changes in serum ALP, AST and ALT activities with alterations in concentrations of total protein, albumin, urea and other serum constituents. Serum bilirubin concentration did not change.