Dhekra Grami

Irinotecan chemotherapy-induced intestinal oxidative stress: Underlying causes of disturbed mucosal water and electrolyte transport

Irinotecan, a chemotherapy drug, can cause acute diarrhea immediately after administration. Hence, the present study was designed to investigate the gastrointestinal (GI) disturbances after an intraperitoneal (IP) administration of irinotecan in rats.Twenty Wistar rats were separated into two groups of ten. Group A was considered as a control group (NaCl, 0.9%). Group B was treated with irinotecan at a single dose of 200mgkg-1. The rats were observed for defecation. For the enteropooling test, the animals were sacrificed by decapitation 1h post-treatment. The small intestine was excised and the fluid was milked into a graduated tube and the volume was measured. After centrifugation of intraluminal liquid, the electrolyte concentrations in the supernatants were measured by flame photometry. Oxidative stress parameters and intracellular mediators as well as the MPO activity were determined in intestinal mucosa by colorimetric methods Our result indicated that irinotecan produces an intestinal fluid accumulation and electrolyte transport disorders. These effects were associated with augmented intestinal MPO activity and oxidative damage such as an elevation of MDA production and a depletion of enzymatic and non-enzymatic antioxidants. More than that, drug administration provoked intracellular mediator disturbances such as a free iron, H2O2 and calcium levels. In conclusion, the data suggest that irinotecan caused a gastrointestinal stress via oxidative stress-induced disturbances in water and electrolyte transport in the intestinal mucosa in rats.

Chemical constituents and pharmacological actions of carob pods and leaves (Ceratonia siliqua L.) on the gastrointestinal tract: A review

Carob tree, Ceratonia siliqua L., is a medicinal plant used in Tunisian traditional medicine for the treatment of the gastro-intestinal (GI) disorders. In this respect, a relatively large number of scientific publications on the carob tree have been published in recent years. Therefore, the present review was aimed to analyze the traditional uses, phytochemical constituents and pharmacological activities of Ceratonia siliqua on the GI tract. Indeed, previous investigations on the carob pods and leaves have revealed the presence of a number of compounds including high amounts of carbohydrates, dietary fibers, minerals, polyphenols, flavonoids and low amounts of protein and lipids. This plant possesses anti-inflammatory, antimicrobial, anti-diarrheique, antioxidant, anti-ulcer, anti-constipation and anti-absorptive of glucose activities in the gastrointestinal tract. Based on the chemical and pharmacological characteristics of C. siliqua, we concluded that this species has beneficial preventive and therapeutic properties, especially, in digestive tract.

Vinblastine, an anticancer drug, causes constipation and oxidative stress as well as others disruptions in intestinal tract in rat

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Ceratonia siliqua L. (immature carob bean) inhibits intestinal glucose absorption, improves glucose tolerance and protects against alloxan-induced diabetes in rat

BACKGROUND This study was designed to investigate the effects of immature carob pod aqueous extract (ICPAE) on intestinal glucose absorption in vitro and in vivo using an oral glucose tolerance test (OGTT) as well as the potential antidiabetic effect in alloxan-induced diabetic rats. OGTT was carried by administration of glucose (2 g kg-1 , p.o.) and after treatment with extract (50, 100 and 200 mg kg-1 body weight). Diabetes was induced by single intraperitoneal injection of alloxan (150 mg kg-1 ). However, the extracts at various doses or glibenclamide (GLB, 10 mg kg-1 body weight) were given by oral administration for 2 weeks. RESULTS ICPAE (50-2000 µg mL-1 ) exerted dose-dependent reduction of sodium-dependent glucose transport across isolated mice jejunum and the maximal inhibition exceeded 50%.The ICPAE treatment improved glucose tolerance. More importantly, ICPAE at various doses showed a significant reduction in blood glucose and biochemical profiles in diabetic rats. CONCLUSION Our findings confirm that the degree of maturity of carob characterized by a different phytochemical composition may be responsible for these actions. Therefore, these compounds may be used as a food supplement in hyperglycemia and diabetes treatments.

Phytochemical properties and pharmacological effects of Quercus ilex L. aqueous extract on gastrointestinal physiological parameters in vitro and in vivo

INTRODUCTION Several research studies have reported on the pharmacological relevance of the medicinal plants used for treating various gastrointestinal disorders and controlling the dietary glucose uptake in the intestinal tract. METHODS Male rats were used to investigate the pharmacological effects of green oak acorn aqueous extract (GOAE) on gastrointestinal physiological parameters in vivo and in vitro. In this respect, the gastro-intestinal motility and hypersecretion essays were evaluated using a simple test meal (10% charcoal in 5% gum arabic) and castor oil induced diarrhea. However, the effect of GOAE on glucose absorption and homeostasis was assessed by the Ussing chamber system and oral glucose tolerance test (OGTT) measures. RESULTS Various doses of the Quercus ilex aqueous extract (125, 250 and 500mgkg-1) administered orally produced a significantly dose-related inhibition of gut meal travel distance in normal rat. The highest intestinal transit reduction of 49.34% was obtained with 500mgkg-1 compared to 58.33% caused by reference drug (clonidine, 1mgkg-1). In castor oil induced diarrhea in rat, Q. ilex extract reduced the frequency of defecation, fluid accumulation and electrolyte transport. These effects were associated with decreased histopathological damage and regulation of intracellular mediators disturbance in the intestinal mucosa. In addition, GOAE treatment improved glucose tolerance and significantly and dose-dependently reduced (>50%) the glucose absorption via intestinal epithelium. Phytochemical screening revealed the presence of many bioactive natural compounds. CONCLUSION These results suggest that the extract was effective towards reducing diarrhea, fluid accumulation, electrolyte transport and glucose absorption, and no toxic effects of the GOAE presented on this study.

Malathion, an organophosphate insecticide, provokes metabolic, histopathologic and molecular disorders in liver and kidney in prepubertal male mice

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Reverse Effect of Opuntia ficus-indica L. Juice and Seeds Aqueous Extract on Gastric Emptying and Small-Bowel Motility in Rat: Prickly pear juice/seeds and GE/GIT…

This study was conducted to compare the effects of juice and seeds on gastric emptying, small-bowel motility and intestinal ion transport. Separate groups of rats were randomized to receive NaCl, increasing doses of juice (5, 10, and 20 mL/kg, b.w.) or seeds aqueous extract (100, 200, and 400 mg/kg, b.w.). Simultaneously, two other groups were received, the reference drugs; clonidine (1 mg/kg) and yohimbine (2 mg/kg). The charcoal meal was used as a suspension for gastrointestinal motility test. The purgative action of juice was confirmed using the loperamide (5 mg/kg, p.o.) induced constipation. To evaluate the antisecretory effect, we were used as a hypersecretion agent, the castor oil at the dose of 5 mL/kg. Compared to the control and standard groups, we were showed that the prickly pear has an opposite effect on small-bowel motility and gastric emptying. Indeed, the juice at various doses has a laxative effect of gastrointestinal transit in healthy and constipated-rats. However, the aqueous extract of the seeds leads to a reduction of motility in normal rats which gives it a remarkable antidiarrhoeal activity, a notable intestinal fluid accumulation decline and electrolyte concentrations reestablishment. Moreover, orally juice administered at different doses accelerated the stomach emptying time in contrast to the seeds aqueous extract. More importantly, a significant variation in the phytochemical constituents levels between juice and seeds was found. These findings confirm the reverse therapeutic effects of this fruit in the treatment of digestive disturbances such as difficulty stool evacuation and massive intestinal secretion, likewise, the gastric emptying process perturbation.

Rosemary (Rosmarinus officinalis) essential oil components exhibit anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects in experimental diabetes

INTRODUCTION The present study aims to investigate the protective effects of Rosemary (Rosmarinus officinalis L.) essential oils (ROEO) against alloxan-induced diabetes and oxidative stress in rats. METHODS The animals were divided into four groups: Healthy Control (HC); Diabetic Control (DC); Healthy+ROEO (H+ROEO) and Diabetic+ROEO (D+ROEO). RESULTS The use of GC/MS technique has allowed us to identify fifteen compounds in ROEO. We have found that alloxan administration induced hyperglycaemia, lipid metabolic parameters deregulation as well as liver and kidney dysfunctions. Alloxan administration has also induced an oxidative stress status as assessed by malondialdehyde (MDA) content increase, thiol groups (-SH) level decrease and antioxidant enzyme activities depletion such as catalase (CAT), total superoxide dismutase (SOD), Cu/Zn-SOD, Mn-SOD and Fe-SOD in both liver and kidney tissues. More importantly subacute (15days) ROEO administration has significantly corrected all biochemical alterations induced by alloxan intoxication. CONCLUSIONS We propose that Rosmarinus officinalis essential oils exhibit protective effects in alloxan-induced hyperglycaemia as well as protecting against liver and kidney oxidative stress in rats, reflecting its antioxidant properties.

Contribution of oxidative stress in acute intestinal mucositis induced by 5 fluorouracil (5-FU) and its pro-drug capecitabine in rats

Abstract This study was designed to examine the contribution of oxidative stress in gastrointestinal disorders after an intraperitoneal administration of 5 fluorouracil (5-FU; 100 mg/kg of body weight (b.w.)) and capecitabine oral administration (500 mg/kg b.w.). The animals were divided into three groups: Group A (NaCl,10 ml/kg of b.w.) considered as control group, group B was intoxicated by 5-FU and group C was the group of animals treated with capecitabine (CAP). To evaluate the secretory and enteropooling effects, we used magnesium sulfate (MgSO4), 1 ml/100 g of b.w. as a hypersecretion agent . The mucosal gastro-intestinal specimens were scraped and examined for biological markers of oxidative stress and intracellular mediators. These anticancer drugs caused many intestinal damages manifested by an elevation of fluid accumulation and imbalance in electrolytes secretion. The intestinal tissues from treated rats not only showed a significant increase in malondialdehyde (MDA), protein carbonylation and hydrogen peroxide (H2O2) production. but also showed a significant depletion of enzymatic and non-enzymatic antioxidant, such as, glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and sulfhydryl groups (-SH). These effects were related with histopathological damage and a perturbation of intracellular mediators. As expected, these disturbances were observed in the group of rats poisoned by the MgSO4. Data suggest the contribution of oxidative stress in chemotherapy-induced many disorders in intestinal tract.

Methotrexate Produces Gastrointestinal Stress via Oxidative Stress-caused Acute Physiological Disruptions in Water and Electrolytes Transport in the Mucosal Intestine

Methotrexate (MTX), a chemotherapeutic agent, is used to treat various types of cancers. MTX was known for its toxic effects, particularly in the gastrointestinal (GI) tract. Consequently, the objective of this present research was to investigate the GI disorders during oxidative stress in rats subjected to oral dose of MTX (100 mg kg21). Thirty male Wistar rats were equally divided at random into three groups (10 animals in each group): the unexposed group and two groups treated with a single dose of MTX. Acute diarrhea was assessed in rats using the defecation and enteropooling methods. Electrolyte levels in intraluminal fluid were analyzed by flame photometry. Oxidative stress indicators and intracellular mediators were determined in mucosal intestine by colorimetric methods. The MTX treatment of rats caused critical changes in the gastrointestinal functions. Mainly, intensification of the liquid stools and intestinal fluid accumulation as well as perturbation in the electrolyte transport was observed. In addition, MTX has a prooxidant effect, which was indicated by an augmentation of malondialdehyde (MDA) and H2O2 generation and a decrease of the enzymatic antioxidants such as SOD, CAT, and GPx. These effects were accompanied with hispathological injury and alteration of lipid metabolism and intracellular mediators such as free iron and calcium. In summary, we found a close association between the gastrointestinal disruptions and the oxidative stress intensity induced by MTX in rats.