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PubMed2001

Khat (Catha edulis) consumption causes genotoxic effects in humans.

We used the micronucleus (MN) test to determine the genetic damage caused by khat, a widely consumed psychostimulant plant, in exfoliated cells of volunteers who chewed the drug on a regular basis. In the first study in which we compared the frequency of MN in buccal and bladder mucosa cells in 20 khat consumers (10-160 g/day) and 10 controls, a pronounced (8-fold) increase in micronucleated buccal mucosa cells was seen among khat consumers; khat consumption did not lead to a detectable elevation of micronucleated bladder mucosa cells. Among heavy khat chewers, 81% of the MN had a centromere signal indicating that khat is aneuploidogenic. To investigate the effect of simultaneous consumption of tobacco and alcoholic beverages, we compared the MN frequency in buccal cells of 25 khat consumers (20-85 g/day) who smoked cigarettes (15-60/day) and drank alcoholic beverages (15-80 g of pure ethanol/day) with a control group (control group I) of 25 individuals matched for age, body weight, tobacco and alcohol consumption and with another control group of 25 individuals (control group II) not consuming any of the drugs. The frequency of buccal mucosa cells with MN was higher in control group I than in group II and the effect of khat, tobacco and alcohol was found to be additive. A time-kinetics study on khat-induced MN showed that the highest frequency of MN was observed during the fourth week after consumption. In light of the large body of evidence on the close association between genetic damage and cancer, these results suggest that khat consumption, especially when accompanied by alcohol and tobacco consumption, might be a potential cause of oral malignancy.

Adult↗
PubMed2000

Mycotoxin-producing potential of fungi associated with qat (Catha edulis) leaves in Yemen.

Forty-four fungal species belonging to 20 genera were isolated from 30 samples of qat leaves. The most frequent genera were Aspergillus, Alternaria, Penicillium, and Cladosporium followed by Fusarium, Drechslera, Chaetomium, and Mucor. The most prevalent species in above genera were Aspergillus niger, A. flavus, A fumigatus, Alternaria alternata, Penicillium chrysogenum, P. citrinum, Cladosporium cladosporioides, and Fusarium verticillioides. From these fungi, 17 species (39%) related to 7 genera (35%) proved to be true endophytes. Eleven out of 75 isolates were mycotoxigenic. A. alternata produced alternariol and alternariol monomethyl ether whereas A. flavus produced aflatoxins B1 and B2. Ochratoxin A, sterigmatocystin, citrinin and T-2 toxin were produced by A. ochraceus, A. versicolor, P. citrinum and F. oxysporum, respectively. The presence of such toxigenic fungi associated with qat leaves is considered to be a threat to public health.

Catha↗
PubMed2005

Determinants of CD4 counts among HIV-negative Ethiopians: role of body mass index, gender, cigarette smoking, khat (Catha Edulis) chewing, and possibly altitude?

To study the determinants of CD4% and CD4 counts among HIV-negative Ethiopians, and to identify factors susceptible to explain the low CD4 counts observed among Ethiopian subjects. Cohort studies among factory workers in Akaki and Wonji, Ethiopia. Clinical and laboratory examinations, including determination of HIV serological status and T-cell subsets, were performed during follow-up visits every six months. In addition, micronutrients (retinol, carotenoids, tocopherol, transferrin receptor, and selenium) plasma concentrations were determined in a subset of 38 HIV-positive and 121 HIV-negative participants. HIV-negative participants with at least one CD4 count measurement were 157 females in Akaki, 203 males in Akaki, and 712 males in Wonji. CD4 counts were independently and positively associated with body mass index (through an increase in lymphocyte counts), female gender (through an increase in CD4%), cigarette smoking (through an increase in CD4%), khat chewing (through an increase in both lymphocyte counts and CD4%), and Akaki study site (through a large increase in lymphocyte counts compensating a decrease in CD4%). Intestinal parasitic infections were not associated with CD4% or CD4 counts. Retinol, carotenoids, and alpha-tocopherol plasma concentrations decreased with HIV infection and advancing immunosuppression, but were not associated with CD4 counts among HIV-negative subjects. Low body mass index among Ethiopians may have contributed to their overall low CD4 counts. Other factors remain to be elucidated.

Adult↗
PubMed1990

The induction of dominant lethal mutations upon chronic administration of khat (Catha edulis) in albino mice.

The mutagenicity of a methanolic extract of khat has been evaluated on male germ cells using the dominant lethal test in albino mice. An aqueous solution of khat extract was administered orally in doses of 50, 100 and 200 mg/kg body wt., respectively, to 3 different groups of male mice for a period of 6 weeks. At the end of treatment each male mouse was allowed to mate with 2 different groups of 3 females each, on 2 consecutive weeks. These females were necropsied on the 13th day of their presumptive mating, and the number of implants in each female and the ratio of live and dead embryos were determined. The results of this study showed that the treatment of male mice over a period of 6 weeks produced a dose-dependent reduction in the rate of fertility in the first week after mating, which was irreversible in the second week at the highest dose (200 mg/kg). Khat extract also induced post-implantation loss during the first week following treatment. However, a comparison of the results of the first and second weeks showed a reversible pattern of dominant lethality.

Animals↗
PubMed1984

Possible involvement of amine oxidase inhibition in the sympathetic activation induced by khat (Catha edulis) chewing in humans.

The possibility that phenylalkylamines (cathinone and cathine) of khat, like amphetamines, are amine oxidase inhibitors with clinical significance is evaluated. Results show that khat chewing induces a significant increase in blood pressure, body temperature and urinary catecholamines in khat naive subjects. On the other hand, in habitual consumers a significant enhancement only of blood pressure is observed. Urinary concentrations of vanilmandelic acid show an inhibitory trend in both groups of subjects. This has been related to a decrease in catecholamine deamination. In fact, oxidative deamination of benzylamine catalyzed by beef plasma amine oxidase is non-competitively inhibited in vitro by cathinone (Ki = 0.05 mM) and cathine (Ki = 10 mM) as well as by amphetamine (Ki = 7.9 mM).

Adult↗
PubMed1995

Effect of (-)-cathinone, a psychoactive alkaloid from khat (Catha edulis Forsk.) and caffeine on sexual behaviour in rats.

The effect of (-)-cathinone, caffeine and their combinations was studied on the sexual behaviour of male rats. Male sexual activities were assessed by recording the erectile responses (grooming of genitalis, yawning/stretching and homosexual mounting), in the absence of females. The copulatory behaviour was observed by caging males with receptive females brought into oestrus with s.c. injection of oestradiol benzoate and progesterone. The copulatory pattern of male rats (mounting, intromissions, ejaculations and refractory period) was recorded. The oral treatment of cathinone (5 mg kg-1 day-1), caffeine (50 mg kg-1 day-1) and their combinations for 15 days increased arousal (motivation) in male rats as evidenced by increased mounting performance and anogenital investigatory behaviour. However, erectile and ejaculatory responses, measured in the present study, showed no stimulant effect. It is conceivable from the present results that cathinone, the psychostimulant constituent of khat modified masculine pattern behaviour and caffeine also changed the effect of cathinone when administered concomitantly. However, our data provide no evidence that cathinone could be considered as an aphrodisiac.

Administration, Oral↗
PubMed2006

Effect of Catha edulis foresk (khat) extracts on male rat sexual behavior.

Khat chewing is a widespread habit that has a deep-rooted socio-cultural tradition in East Africa and in the Middle East. Although a number of investigations have been carried out using cathinone, the psychoactive component of khat, these may not wholly reflect the behavioral effects observed after administering khat in a dosage similar to those used traditionally. The aim of the present study was to evaluate the effect of sub-chronically administered khat extract with or without alcohol on sexual behavior in male rats. Adult albino wistar male rats were administered either with khat extracts (100, 200, 400mg/kg), amphetamine (1mg/kg), sildenafil (1mg/kg), ethanol (2ml/kg of 2% and 10%), or a combination of khat and ethanol (2%+10%) by intragastric gavage orally for 15 days. Khat (400mg/kg) treated rats demonstrated a statistically significant increase in all sexual parameters except in mounting frequency, intercopulatory interval and copulatory efficiency. Whereas, khat (200mg/kg) treated rats showed a statistically significant increase only in ejaculation latency (P<0.01). In marked contrast, low dose (100mg/kg) of khat extract was found to significantly reduce both mount latency (P<0.05) and intromission latency P<0.01) thereby enhancing sexual motivation/arousal in male rats. Similar results were obtained when khat extract (200mg/kg) and ethanol (10%) were administered concomitantly despite the inhibitory effect observed in male sexual behavior when administered alone. From the present study it can be concluded that higher doses of the extract inhibit sexual behavior in male rats. In contrast, low dose of the extract as well as the concurrent administration of the extract followed by ethanol was found to enhance male rat sexual motivation/arousal.

Amphetamine↗
PubMed2000

Fluoride content in khat (Catha edulis) chewing leaves.

Khat (qat) leaves are chewed for their psychostimulative effects; there is an unconfirmed suggestion that they contain a high concentration of fluoride (F). Khat samples from Yemen were suspended in deionized water, spun, and the supernatants exposed to a chelator that decomplexes F, which was assayed with an F(-)-electrode coupled to an ion analyser. F released into whole saliva after chewing khat for 15 min and from khat suspended in stimulated whole saliva for 1.5 h in vitro was measured also. Total F in dried khat leaves and their ash was assayed by the acid-hexamethyldisiloxane microdiffusion method. All methods demonstrated negligible amounts of F in or from khat leaves (<0.02 microg F/ml leached into water or saliva; 0.06 microg F/ml in saliva after chewing; 0.93 microg total F/g in dried leaf, 2.07 microg total F/g in ash).

Catha↗
PubMed2003

Effect of Catha edulis on plasma glucose and C-peptide in both type 2 diabetics and non-diabetics.

In this study, the effect of regular khat chewing on serum glucose and C-peptide levels were investigated in both healthy male individuals and type 2 diabetic patients. The results presented show the levels of glucose and C-peptide of healthy individuals to be non-significantly different between khat and non-khat chewers which may be due to the rapid release of insulin which prevents the sympathetic khat effect on rising serum glucose. On comparing both diabetic groups, those of khat chewers showed a non-significant increase of glucose levels at 0, 1 and 2 h of khat chewing. However, the non-significant increase of serum glucose at 1 h of khat chewing corresponded with a significant increase of serum C-peptide (22%) levels. On selecting the base-line glucose of diabetic individuals between 200 and 450 mg/dl, both diabetic khat and non-khat chewers still showed no significant difference in serum glucose and C-peptide at 2 h post-meal. However, serum glucose was seen to be significantly higher in the khat chewers by 32.1 and 32.6% after 1 and 2 h of khat chewing, respectively. Along the same line, serum C-peptide was higher in the khat chewers by 39.4 and 12.9% at 1 and 2 h of khat chewing, though not significantly. In conclusion, chronic khat chewing does not affect serum glucose and C-peptide in healthy individuals while it increases glucose and C-peptide levels during the khat session in diabetic individuals especially those having serum glucose between 200 and 450 mg/dl at 2 h post-meal.

Adult↗
PubMed1991

The toxicity of Catha edulis (khat) in mice.

A large number of people in East Africa and Southern Arabia chew khat leaves because of its pleasurable and stimulating effects. Due to its habit forming property, the khat has been classified as a "Substance of Abuse" by the World Health Organization. In view of the large number of medical problems reported in khat chewers, the present study was undertaken to investigate the chronic toxicity of khat in mice. Three groups of mice were treated with aqueous solution of khat extract in the dose of 50, 100, and 200 mg/kg. body weight daily by oral intubation route for 6 weeks. The results indicated a dose-dependent decrease in body weight, an increase in the incidence of mortality and induction of site specific body and eye lesions. The histopathological examination of the lesions revealed reactive hyperplasia and necrosis in the lymphoid tissues. The necrotic areas in the subcutaneous tissues showed the presence of numerous polymorphs.

Animals↗
PubMed1989

Use and abuse of khat (Catha edulis): a review of the distribution, pharmacology, side effects and a description of psychosis attributed to khat chewing.

There have been relatively few reported cases of psychosis due to khat usage despite its heavy consumption in certain East African and Arabian countries. Four cases have been reported in the UK. We report here on three further cases of psychotic reactions to this substance in Somalian males, and emphasize the need to be aware of khat as a potential substance of abuse, with both medical and psychiatric complications. The features of khat psychoses are described and the relationship to amphetamine and ephedrine psychoses is discussed. The forensic aspects of two of the cases which involved homicide and combined homicide and suicide are highlighted, as is the possible role of social dislocation from the culture of origin.

Adult↗
PubMed2004

Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells.

Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition in Africa and the Middle East. The biological effects of khat are inadequately investigated and controversial. For the first time, we show that an organic extract of khat induces a selective type of cell death having all morphological and biochemical features of apoptotic cell death. Khat extract was shown to contain the major alkaloid compounds cathinone and cathine. The compounds alone and in combination also induced apoptosis. Khat-induced apoptosis occurred synchronously in various human cell lines (HL-60, NB4, Jurkat) within 8 h of exposure. It was partially reversed after removal of khat and the effect was dependent on de novo protein synthesis, as demonstrated by cotreatment with cycloheximide. The cell death was blocked by the pan-caspase inhibitor Z-VAD-fmk, and also by submicromolar concentrations of Z-YVAD-fmk and Z-IETD-fmk, inhibitors of caspase-1 and -8, respectively. The 50% inhibition constant (IC(50)) for khat (200 microg ml(-1))-induced apoptosis by Z-VAD-fmk, Z-YVAD-fmk and Z-IETD-fmk was 8 x 10(-7) M as compared to 2 x 10(-8) M and 8 x 10(-8) M, respectively. Western blot analysis showed a specific cleavage of procaspase-3 in apoptotic cells, which was inhibited by Z-VAD-fmk. The cell death by khat was more sensitively induced in leukaemia cell lines than in human peripheral blood leukocytes. It is concluded that khat induces a rather swift and sensitive cell death by apoptosis through mechanisms involving activation of caspase-1, -3 and -8.

Amino Acid Chloromethyl Ketones↗