Antidiarrheal and Antibacterial Activities of Monterey Cypress Phytochemicals: In Vivo and In Vitro Approach.

Monterey cypress (Cupressus macrocarpa) is a decorative plant; however, it possesses various pharmacological activities. Therefore, we explored the phytochemical profile of C. macrocarpa root methanol extract (CRME) for the first time. Moreover, we investigated its antidiarrheal (in vivo), antibacterial, and antibiofilm (in vitro) activities against Salmonella enterica clinical isolates. The LC-ESI-MS/MS analysis of CRME detected the presence of 39 compounds, besides isolation of 2,3,2″,3″-tetrahydro-4'-O-methyl amentoflavone, amentoflavone, and dihydrokaempferol-3-O-α-l-rhamnoside for the first time. Dihydrokaempferol-3-O-α-l-rhamnoside presented the highest antimicrobial activity and the range of values of MICs against S. enterica isolates was from 64 to 256 µg/mL. The antidiarrheal activity of CRME was investigated by induction of diarrhea using castor oil, and exhibited a significant reduction in diarrhea and defecation frequency at all doses, enteropooling (at 400 mg/kg), and gastrointestinal motility (at 200, 400 mg/kg) in mice. The antidiarrheal index of CRME increased in a dose-dependent manner. The effect of CRME on various membrane characters of S. enterica was studied after typing the isolates by ERIC-PCR. Its impact on efflux and its antibiofilm activity were inspected. The biofilm morphology was observed using light and scanning electron microscopes. The effect on efflux activity and biofilm formation was further elucidated using qRT-PCR. A significant increase in inner and outer membrane permeability and a significant decrease in integrity and depolarization (using flow cytometry) were detected with variable percentages. Furthermore, a significant reduction in efflux and biofilm formation was observed. Therefore, CRME could be a promising source for treatment of gastrointestinal tract diseases.

Evaluation of Anti-Diarrheal Activity of Methanol Root Bark Extract of Milicia Excelsa (Welw) C. C Berg (Moraceae) in Rats.

Milicia excelsa (Moraceae) plant is used as an antidiarrheal agent in ethnomedicine but there is no scientific rationale for its claim. Hence, this study examined the acute toxicity (LD50) and anti-diarrheal effect of methanol root bark extract of Milicia excelsa per oral in rats as well as the probable phytoconstituents responsible for this effect. The LD50 was>5000 mg/kg, suggesting its safety. The extract significantly (p<0.05) reduced the total number of feces and wet feces in castor oil-induced diarrhea with percentage inhibitions of 41.36 and 50.88% at 200 and 400 mg/kg respectively; it also significantly (p<0.05) reduced the distance travelled by charcoal in a dose dependent manner with percentage inhibitions of 33.85, 43.07 and 50.76% at 100, 200 and 400 mg/kg respectively in gastrointestinal motility test indicating anti-diarrheal potentials. The extract significantly (p<0.05) reduced the intestinal fluid accumulation with percentage inhibitions of 33.28 and 45.61% at 200 and 400 mg/kg respectively, suggesting antisecretory effect. Furthermore, the extract significantly (p<0.05) inhibited the intestinal propulsion of the charcoal meal through the gastrointestinal tract in castor oil-induced gastrointestinal transit suggesting antimotility effect. Total flavonoids and tannins are the most abundant phytoconstituents therein. This study therefore concluded that the anti-diarrhea action of the extract may at least in part be mediated via antisecretory and antimotility mechanisms, which could be due to the additive, synergy or counter interaction of the phytoconstituents therein, thus supporting its ethnomedicinal claim.

Emodin-induced hepatotoxicity was exacerbated by probenecid through inhibiting UGTs and MRP2.

Aggravating effect of probenecid (a traditional anti-gout agent) on emodin-induced hepatotoxicity was evaluated in this study. 33.3% rats died in combination group, while no death was observed in rats treated with emodin alone or probenecid alone, indicating that emodin-induced (150 mg/kg) hepatotoxicity was exacerbated by probenecid (100 mg/kg). In toxicokinetics-toxicodynamics (TK-TD) study, aspartate aminotransferase (AST) and systemic exposure (area under the serum concentration-time curve, AUC) of emodin and its glucuronide were significantly increased in rats after co-administrated with emodin and probenecid for 28 consecutive days. Results showed that the increased AUC (increased by 85.9%) of emodin was mainly caused by the decreased enzyme activity of UDP-glucuronosyltransferases (UGTs, decreased by 11.8%-58.1%). In addition, AUC of emodin glucuronide was increased 5-fold, which was attributed to the decrease of multidrug-resistant-protein 2 (MRP2) protein levels (decreased by 54.4%). Similarly, in vitro experiments proved that probenecid reduced the cell viability of emodin-treated HepG2 cells through inhibiting UGT1A9, UGT2B7 and MRP2. Our findings demonstrated that emodin-induced hepatoxicity was exacerbated by probenecid through inhibition of UGTs and MRP2 in vivo and in vitro, indicating that gout patients should avoid taking emodin-containing preparations in combination with probenecid for a long time.

Generational reproductive outcomes in Wistar rats maternally exposed to Ricinus communis oil at different stages of gestation.

Fetal programming hypothesis presupposes that stimulus or insult acting during critical periods of uterine growth and development may permanently alter tissue structure and function. Ricinus communis oil (RCO) has been reported to possess/used as laxative, labor-inducing and estrogenic properties. Generational reproductive effects of maternal exposure to RCO was investigated in rats. A total of 25 pregnant rats randomly assigned to five equal groups were treated with distilled water (control, group 1), RCO (950 mg/kg p.o.) during gestation days (GD) 1-7, 7-14, 14-21 and 1-21, respectively. Birth weight, morphometric data, anogenital distance (AGD), pubertal age, sperm parameters, hormonal profile, organ weight and histopathology were determined in the first (F1) and second (F2) filial generations. Results showed a significant decrease (P<0.05) in birth weight/morphometric data in male pups from the GD 1-7 and 7-14 groups. AGD decreased significantly in RCO-treated F1 males. Pubertal age of F1 females decreased significantly (P<0.05) compared with controls. At postnatal day 90, F1 males from the RCO-treated group showed significant decrease in testis weight, body weight, sperm count, motility and normal morphology. Testosterone levels were significantly decreased in RCO-treated F1 males, which also showed testicular interstitial edema and epididymal hypospermia. Only pubertal indexes were altered in F2 rats. Maternal exposure to RCO at early gestation periods impaired androgen-mediated reproductive end points in the first generation of rats. RCO exhibits endocrine disrupting capabilities.

Protective effect of Dalbergia sissoo Roxb. ex DC. (family: Fabaceae) leaves against experimentally induced diarrhoea and peristalsis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia sissoo Roxb. ex DC. (family: Fabaceae; Indian Rosewood), is used in India, especially in rural communities by traditional medicine practitioners to treat diarrhoea. However, scientific evidence does not exist in any literature to substantiate the claim of therapeutic success of the plant species in diarrhoea. AIM: To study the protective effect of ethanol extract from D. sissoo Roxb. ex DC. leaves (EDSL) against experimentally induced diarrhoea and peristalsis in mice. MATERIALS AND METHODS: Castor oil-induced diarrhoea and magnesium sulphate (MgSO4)-induced diarrhoea tests were used to assess the antidiarrhoeal activity of D. sissoo. Gastrointestinal tract transit of charcoal meal test and barium sulphate milk was used to assess the peristalsis activity of the extract, while the acute toxicity study and determination of total phenolics and total flavonoids were carried out using well-established protocols and methods. RESULTS: The EDSL significantly reduced faecal output in castor oil-induced and MgSO4-induced diarrhoea and also significantly reduced the number of diarrhoeal episodes. D. sissoo significantly delayed the onset of diarrhoea induced by both castor oil and MgSO4 and comparable to loperamide, a standard antidiarrhoeal drug. Both D. sissoo and atropine sulphate significantly reduced the peristalsis activity of charcoal meal and barium sulphate milk in mice. The preliminary phytochemical analysis of EDSL revealed the presence of carbohydrates, phenolics, glycosides, and flavonoids. The median lethal dose of EDSL was greater than 2000 mg/kg (orally (p.o.)). CONCLUSION: The data obtained indicate that the EDSL has antidiarrhoeal and antiperistalsis activities and thus supports its traditional use. The data also show that the plant material given p.o. may be safe and/or non-toxic in mice.

[Serious risk related to oral use of sodium phosphate solution]. / Závazná rizika spojená s uzíváním natrium-fosfátových projímadel.

Sodium phosphate solutions are commonly used to cleanse the bowel in preparation for colonoscopy, for barium enema or surgical procedures and eventually for treatment of severe constipation. Though relatively safe, these drugs must be used with caution in patients with kidney disease, small intestinal disorders, or poor gut motility and are prohibited in renal insufficiency and bowel obstruction. Especially elderly patients are at increased risk for phosphate intoxication due to decreased glomerular filtration rate, concomitant medication use, and systemic and gastrointestinal diseases. Sodium phosphate solution could induce by at-risk patients serious electrolyte abnormalities (hyperphosphatemia, hypocalcemia, hypokalemia) and acute kidney injury called acute phosphate nephropathy, which is potentially life-threatening condition with slowly progressive renal insufficiency. This article gives a report on two cases of severe adverse effects after administration of oral sodium phosphate solution: an elderly women who developed increase in serum phosphate with compensatory severe hypokalcemia with tetany; and an elderly man who developed acute phosphate nephropathy following colon preparation prior to colonoscopy and barium enema. Especially in elderly and in patients in whom sodium phosphate solution is contraindicated or should be used with caution, we recommend to use isosmotic macrogol (polyethylene glycol) solution for the bowel cleansing a for the treatment of constipation.

Antimotility effects of extracts and fractions of Eastern Nigeria mistletoe (Loranthus micranthus Linn).

OBJECTIVE: To evaluate the antimotility activity of Eastern Nigerian mistletoe[Loranthus micranthus (L. micranthus) Linn] parasitic on six different host trees viz. Baphia nitida, Persia americana, Kola accuminata, Irvingia gabonensis, Citrus simensis and Pentacletra macrophylla (P. mycrophylla). METHODS: The antimotility of the methanol extracts and solvent fractions were evaluated in castor oil induced diarrheoa in rats. RESULTS: The methanol extracts (200 mg/kg, i.p.) inhibited defeacation significantly (P < 0.05) 4 h after administration (75.73% to 93.33%) more than that of atropine sulphate (2 mg/kg, i.p.) which inhibited defeacation by 80.0%. The methanol extract (200 mg/kg, i.p.) of L. micranthus parasitic on P. mycrophylla exhibited significant (P<0.05) inhibition in gastrointestinal transit (67.6%) more than that of atropine sulphate (2 mg/kg, i.p.) which inhibited gastrointestinal transit by 26.4%. The solvent fractions of L. micranthus parasitic on P. mycrophylla at dose levels of 150 mg/kg inhibited significantly the gastrointestinal transit of mice. Fraction F(5) exhibited inhibitory activity which was comparable to loperamide (73.3%). CONCLUSION: The methanol extract of L. micranthus parasitic on P. macrophylla exhibits higher antimotility activity that other extracts. The solvent fractions could serve as source of novel antimotility agents.

Mechanism of action and toxicities of purgatives used for colonoscopy preparation.

IMPORTANCE OF THE FIELD: In developed countries, colonoscopy volume has increased dramatically over the past 15 years and is the principle method used to screen for colon cancer. Preparations used for colon cleaning have evolved over the past 30 years. Some preparations have been shown to be unsafe and are now used on a limited basis. There has been progress on limiting the volume required and on taste improvement. AREAS COVERED IN THIS REVIEW: This review provides an account of preparations used from 1980 when PEG-based preparations became widely available, until the present day. The review highlights their mechanism of action and principle toxicities. The handling of solutes and solute-free fluid by the colon is also reviewed. WHAT THE READER WILL GAIN: The reader will gain a perspective on the factors considered in developing colonic purgatives and the rationale for choosing selected preparations based on patient factors such as age, co-morbidities and concomitant medications. TAKE HOME MESSAGE: Although generally safe and effective, colonic purgatives have both acute and permanent toxicities. The safest preparations utilize PEG combined with a balanced electrolyte solution. Limitations of this preparation center on the volume required and poor taste. Alternative formulations are now available; however, those using sodium phosphate have fallen out of favor due to a risk of renal toxicity.

Bioenergetic effects of sodium sulfate on the freshwater crustacean, Ceriodaphnia dubia.

I tested the hypothesis that if sodium sulfate alters the bioenergetics of Ceriodaphnia dubia, concentrations that cause reduced fecundity in the short (7-day) and long (5 generations) term should also cause changes in feeding rate and/or metabolism, measured as oxygen consumption. In addition, to test the hypothesis that an altered bioenergetic level caused by sodium sulfate exposure will affect the response of that organism to another toxicant, I measured the acute toxicity of phenol to C. dubia in the presence and absence of both food and sodium sulfate. Sodium sulfate reduced the filter-feeding rate of C. dubia, which was associated with significantly reduced oxygen consumption. This decreased energy level appeared to result in a consistent but decreased level of fecundity over a number of generations and the reproductive impairment was dose-dependent. These effects occurred at concentrations much lower than those at which acute (mortality) effects have been observed, a finding that may have regulatory implications. In addition, whereas phenol toxicity to C. dubia was exacerbated by the addition of food, increased phenol toxicity, likely induced by an increase in filtering or metabolic rate due to food addition, was negated when sodium sulfate was added to the test medium.

An oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the rat.

Senna (Tinnevelly senna fruits), a known laxative derived from plants, was administered by gavage to Sprague-Dawley (Crl:CD (SD) BR) rats once daily at dose levels of 0, 25, 100 and 300 mg/kg/day for up to 104 consecutive weeks. Based upon clinical signs related to the laxation effect of senna, the highest dose (300 mg/kg/day) was considered to be a maximum tolerated dose. Sixty animals per sex were assigned to the control and dose groups. Assessments included clinical chemistry, hematology, full histology (control and high-dose groups; in addition, low and mid dose: intestinal tract, adrenals, liver, kidneys, brain and gross lesions) and toxicokinetics. The primary treatment-related clinical observation was mucoid feces seen at 300 mg/kg/day. When compared to controls, animals administered 300 mg/kg/day had slightly reduced body weights, increased water consumption and notable changes in electrolytes in serum (increases in potassium and chloride) and urine (decreases in sodium, potassium and chloride). The changes in electrolytes are most likely physiologic adaptations to the laxative effect of senna. At necropsy, dark discoloration of the kidneys was observed in animals in all treated groups. Histological changes were seen in the kidneys of animals from all treated groups and included slight to moderate tubular basophilia and tubular pigment deposits. In addition, for all treated groups, minimal to slight hyperplasia was evident in the colon and cecum. These histological changes, together with the changes seen in the evaluation of clinical chemistry and urine parameters, have been shown to be reversible in a previous 13-week rat study of senna. No treatment-related neoplastic changes were observed in any of the examined organs. Based upon these data, it is concluded that senna is not carcinogenic even after daily administration for 2 years at dosages of up to 300 mg/kg/day in Sprague-Dawley rats.

Phenolphthalein and bisacodyl: assessment of genotoxic and carcinogenic responses in heterozygous p53 (+/-) mice and syrian hamster embryo (SHE) assay.

Phenolphthalein (800 and 2400 mg/kg/day by gavage and 2400 mg/kg/day by diet) and bisacodyl (800-500, 4000-2000, and 8000 mg/kg/day by gavage) were administered to 15 male and 15 female and 20 male and 20 female p53(+/-) mice respectively for 26 weeks to investigate the potential carcinogenicity of each compound. Toxicokinetic analyses confirmed systemic exposure. p-Cresidine was administered by gavage (400 mg/kg/day) and served as the positive control agent in each study. Dietary phenolphthalein reduced survival in both sexes and early deaths were attributed to thymic lymphoma. No bisacodyl-related neoplasms were observed. Regardless of route of administration to p53(+/-) mice, phenolphthalein but not bisacodyl was unequivocally genotoxic, causing increased micronuclei in polychromatic erythrocytes. In the Syrian hamster embryo (SHE) cell transformation assay, phenolphthalein caused increases in morphologically transformed colonies, thereby corroborating NTP's earlier reports, showing phenolophthalein has potential carcinogenic activity. Bisacodyl was negative in the SHE assay. Results of these experiments confirm an earlier demonstration that dietary phenolphthalein causes thymic lymphoma in p53(+/-) mice and show that (1) phenolphthalein causes qualitatively identical results in this transgenic model regardless of route of oral administration, (2) phenolphthalein shows evidence of micronucleus induction in p53(+/-) mice for up to 26 weeks, (3) phenolphthalein induced transformations in the in vitro SHE assay, and (4) bisacodyl in p53(+/-) mice induces neither drug-related neoplasm, nor micronuclei in polychromatic erythrocytes, and did not induce transformations in the in vitro SHE assay.

Spasmogenic activity and acute toxicity of Yumijangquebo, a herbal laxative formulation.

We evaluated the pharmacological properties and spasmogenic activities of Yumijangquebotrade mark, a Korean herbal laxative formulation. Doses in the range 12-50 microg/ml induced a large spasmogenic effect in isolated guinea pig ileum, similar to that induced by acetylcholine. Pre-treating the tissue with atropine (0.2 microM) completely abolished the contractile effect of Yumijangquebo. The spasmogenic effect of Yumijangquebo and the inhibition of this effect by atropine suggest that a cholinergic mechanism is responsible for its effects. Yumijangquebo increased the gastrointestinal motility in ICR mice at doses between 10 and 37 mg/kg. Yumijangquebo exhibited higher activity than three other laxatives tested, which had activities about 85% of that of Yumijangquebo. In an acute toxicity study using Sprague-Dawley rats, the median lethal dose (LD50) of Yumijangquebo was greater than 2000 mg/kg, and we found no pathological changes in macroscopic examination by necropsy of rats treated with Yumijangquebo. We conclude that Yumijangquebo may be safely used as a herbal spasmogenic laxative agent.

A 13-week oral toxicity study of senna in the rat with an 8-week recovery period.

Senna was administered by gavage to Sprague Dawley rats once daily at dose levels of 0, 100, 300, 750 or 1500 mg/kg for up to 13 consecutive weeks followed by an 8-week recovery period for selected animals. Dose- and treatment-related clinical signs included abnormal feces, which were seen to varying degrees from animals at 300 mg/kg per day and more. Animals receiving 750 or 1500 mg/kg per day had significantly reduced body weight gain (males only) and, related to the laxative properties of senna, increased water consumption and notable changes in electrolytes in both serum and urine. At both the terminal and recovery phase necropsy, an increase in absolute and relative kidney weights was seen for male and female animals receiving 750 and/or 1500 mg/kg per day. A dark discoloration of the kidneys was observed at necropsy along with histopathological changes in the kidneys (slight to moderate tubular basophilia and pigment deposits) at 300 mg/kg and above. However, there were no indications in laboratory parameters of any renal dysfunction. In addition, for all treated groups, minimal to slight hyperplasia was recorded in the forestomach and large intestine. Following 8 weeks of recovery, with the exception of the brown pigment in the kidneys, there were no histopathological abnormalities. Thus, the biochemical and morphological changes seen following 13 weeks of treatment of senna significantly reversed following 8 weeks of recovery.

Biodynamic constituents in the Mexican morning glories: purgative remedies transcending boundaries.

Jalap, a pre-Hispanic herbal remedy still considered a useful laxative, is an ingredient in some over-the-counter products sold by herbalists in contemporary Mexico. The purgative crude drugs are prepared from the roots of several morning glories species which all have been identified as members of the Ipomoea genus (Convolvulaceae). Their incorporation as therapeutical agents into Europe is an outstanding example of the assimilation of botanical drugs from the Americas as substitutes for traditional Old World remedies. Phytochemical investigations on the resin glycosides, main constituents of these drugs, were initiated during the second half of the XIX century; however, the structures of their active ingredients had remained poorly known, and still are for some members of these purgative root species. Modern analytical techniques with higher resolution capabilities (HPLC) for the isolation of the active principles of these crude drugs used in conjunction with powerful spectroscopic methods (high field NMR) have facilitated the investigation of these relevant, to the herbal product market, convolvulaceous species during the last decade. The advantages and limitations of theses techniques will be discussed. This review will also describe the ethnobotanical information associated with the Mexican morning glory species and how the traditional usages of these plants have played an important role in the selection of these materials for chemical studies. Little is as yet known about either the mechanism of purge action caused by the resin glycosides or the ecological significance of these same compounds for the producing plants. Over the five centuries of Mexican herbal medicine, one hundred years of phytochemistry has only partially elucidated the active ingredients of the jalap roots but has exemplified how to further contemporary drug discoveries through the investigation of those plants traditionally held to be economically and medicinally important in developing countries.

Acute toxicity and mutagenicity study on branched corn syrup and evaluation of its laxative effect in humans.

We developed a branched corn syrup (BCS, average molecular weight: 500, content of indigestible portion: 45%) by heat treatment of indigestible dextrin with hydrochloric acid. To confirm the safety of BCS, we conducted both an acute toxicity test and a mutagenicity test. Moreover, we observed gastroenteric effects of BCS in fifty healthy humans. The results are summarized as follows. 1) There was no death observed after oral administration of BCS in Sprague-Dawley-strain rats. Lethal dose (LD)50, value was estimated to be more than 10 g/kg body weight. 2) No mutagenicity was observed in Salmonella typhimurium TA98, TA100, TA1535, TA1537, or Escherichia coli WP2uvrA. 3) Fifty adults were divided into five groups often (five of each sex) and orally administered BCS at 0.2, 0.3, 0.4. 0.5 and 0.6 g/kg body weight as indigestible portion. Although no diarrhea was observed in females, BCS at 0.6 g/kg as indigestible portion caused diarrhea in two out of five males. The maximum non-effective dose of indigestible portion of BCS was estimated to be 0.5 g/kg in males and more than 0.6 g/kg in females.

Induction of chromosome aberrations in vitro by phenolphthalein: mechanistic studies.

Phenolphthalein induces tumors in rodents but because it is negative in assays for mutation in Salmonella and in mammalian cells, for DNA adducts and for DNA strand breaks, its primary mechanism does not seem to be DNA damage. Chromosome aberration (Ab) induction by phenolphthalein in vitro is associated with marked cytotoxicity. At very high doses, phenolphthalein induces weak increases in micronuclei (MN) in mouse bone marrow; a larger response is seen with chronic treatment. All this suggests genotoxicity is a secondary effect that may not occur at lower doses. In heterozygous TSG-p53((R)) mice, phenolphthalein induces lymphomas and also MN, many with kinetochores (K), implying chromosome loss. Induction of aneuploidy would be compatible with the loss of the normal p53 gene seen in the lymphomas. Here we address some of the postulated mechanisms of genotoxicity in vitro, including metabolic activation, inhibition of thymidylate synthetase, cytotoxicity, oxidative stress, DNA damage and aneuploidy. We show clearly that phenolphthalein does not require metabolic activation by S9 to induce Abs. Inhibition of thymidylate synthetase is an unlikely mechanism, since thymidine did not prevent Ab induction by phenolphthalein. Phenolphthalein dramatically inhibited DNA synthesis, in common with many non-DNA reactive chemicals that induce Abs at cytotoxic doses. Phenolphthalein strongly enhances levels of intracellular oxygen radicals (ROS). The radical scavenger DMSO suppresses phenolphthalein-induced toxicity and Abs whereas H(2)O(2) potentiates them, suggesting a role for peroxidative activation. Phenolphthalein did not produce DNA strand breaks in rat hepatocytes or DNA adducts in Chinese hamster ovary (CHO) cells. All the evidence points to an indirect mechanism for Abs that is unlikely to operate at low doses of phenolphthalein. We also found that phenolphthalein induces mitotic abnormalities and MN with kinetochores in vitro. These are also enhanced by H(2)O(2) and suppressed by DMSO. Our findings suggest that induction of Abs in vitro is a high-dose effect in oxidatively stressed cells and may thus have a threshold. There may be more than one mechanism operating in vitro and in vivo, possibly indirect genotoxicity at high doses and also chromosome loss, both of which would likely have a threshold.

Mitochondrial metabolism impairment in muscle fibres of rats chronically intoxicated with Senna occidentalis seeds.

The chronic administration of S. occidentalis seeds was found to induce a mitochondrial myopathy in hens. This study was undertaken to determine if the chronic treatment with S. occidentalis seeds of rats (as a mammalian model) would induce a mitochondrial myopathy similar to those described in humans and to determine if the histological changes could be correlated with the amount of ingested seeds. Twenty-one days old rats were fed S. occidentalis seeds at different diet concentrations (1, 2, 3%). Rats fed 1% S. occidentalis seeds had only a few COX-negative muscle fibers in the pectoralis major muscle. Rats fed 3% Senna occidentalis seeds had a greater number of COX-negative fibers. Rats fed 2% had an intermediate number of COX-negative fibers. Activity of SDH and NADH-tr were decreased in rats of groups 2% and 3%. Our data indicate that a progressive mitochondrial metabolism impairment can be produced in rats fed S. occidentalis seeds and that this impairment can be correlated with the amount of ingested seeds.