Anti-inflammatory Effects of Deuterium-Depleted Water Plus Rosa Damascena Mill. Essential Oil Via Cyclooxygenase-2 Pathway in Rats.

OBJECTIVES: Natural medicine has been proposed for treating sepsis worldwide. Therefore, in this study, the effect of deuterium-depleted water (DDW) alone and adjuvant with Rosa damascena Mill. (RD) essential oils was considered through the evaluation of oxidative stress-antioxidant parameters and the expression of cyclooxygenase-2 (COX-2) inflammatory gene in liver damage caused by sepsis. MATERIALS AND METHODS: The rats were randomly divided into 5 groups: 1) laparotomy group; 2) cecal ligation and puncture (CLP) group; 3) DDW (15 ppm and 30 ppm doses) group; 4) DDW (15 ppm and 30 ppm doses) plus RD essential oil (100 mg/kg.bw); 5) indomethacin (2 mg/kg.bw) as a positive control. The treatments were daily administrated for 2 weeks and the CLP model was created on the day 15. Then, the animals were killed and their liver tissue was separated for histopathologic and biochemical assessment. RESULTS: Our results demonstrated that the treatment of animals with DDW and DDW plus RD essential oil was effective due to the regulation of the oxidative stress-antioxidant parameters including lipid peroxidation, glutathione (GSH), GSH s-transferases, myeloperoxidase, ferric reducing ability of plasma and inflammatory parameters such as prostaglandin E2 and COX-2. Pathological studies also showed that sepsis led to the liver tissue injuries, which can be reduced by treatments. CONCLUSION: Sepsis caused oxidative stress in the liver tissue, but the administration of DDW and DDW plus RD essential oil can be useful to prevent and heal these injuries.

Considering the Effect of Rosa damascena Mill. Essential Oil on Oxidative Stress and COX-2 Gene Expression in the Liver of Septic Rats.

OBJECTIVES: Sepsis is a clinical illness with a high rate of mortality all over the world. Oxidative stress is considered the main phenomenon that occurs in sepsis. Rosa damascena Mill. is an ancient herbal plant with high pharmacological activities. MATERIALS AND METHODS: Cecal ligation and puncture (CLP) as a standard model was used to induce sepsis in rats. Male adult rats were randomly divided into 5 groups. Different doses of R. damascena essential oil (50 and 100 mg/kg.bw) were gavaged orally for 14 days and on day 15 CLP was performed. After 24 h, blood samples and liver tissues were removed in order to measure oxidative stress [myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), glutathione-S-transferase, and ferric reducing ability of plasma (FRAP)] and biochemical parameters [alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), and bilirubin] together with plasma prostaglandin E2 (PGE2) and COX-2 expression. RESULTS: The essential oil was capable of modulating all of the oxidative stress, antioxidant, and anti-inflammatory parameters induced by CLP as characterized by elevations in MPO and MDA levels as well as increases in AST and ALT concentrations concomitant with PGE2 and COX-2 increments. The antioxidant defense system such as GSH and FRAP was also increased in the essential oil treated groups. CONCLUSION: Our results showed that the essential oil has antioxidative and hepatoprotective activities through reducing the oxidative injury in sepsis caused by CLP.

Assessing the effect of Mentha longifolia essential oils on COX-2 expression in animal model of sepsis induced by caecal ligation and puncture.

CONTEXT: Mentha longifolia L. (Lamiaceae), a traditional Iranian plant, possesses antimicrobial and antioxidant activities. OBJECTIVE: We investigated the potential protective effects of M. longifolia essential oils (E.Os) on caecal ligation and puncture (CLP) induced liver injury. MATERIALS AND METHODS: Wistar Albino rats (n = 50) were grouped as follows: (1) a laparotomy group (LAP); (2) a CLP group (CLP); (3) the treatment groups received orally the E.Os (50 and 100 mg/kg b.w) and indomethacin (2 mg/kg b.w) for 2 weeks. The oxidative stress parameters, liver enzymes and prostaglandin E2 (PGE2) level were measured in liver and plasma tissues. The liver was also harvested for the real time PCR of cyclooxygenase (COX-2) expression following histopathological examinations. RESULTS: The results indicated that the CLP operation significantly increased lipid peroxidation (LP) [1.79-fold], myeloperoxidase (MPO) [2.76-fold], PGE2 [1.56-fold] besides plasma aspartate aminotransferase (AST) [2.4-fold] and alanine aminotransferase (ALT) activities [2.22-fold], while, markedly reduced glutathione (GSH) [0.63-fold] and ferric reducing ability of plasma (FRAP) levels [0.63-fold]. Even COX2 expression significantly increased in the CLP group as compared to the LAP group. Treatments of rats with the E.Os could return all the hepatic and plasma biomarkers to the normal levels. These results were further confirmed by pathological examination on liver indicating that E.Os could successfully improve the CLP-induced liver injuries. DISCUSSION AND CONCLUSIONS: Our findings suggest that E.Os is able to protect liver injuries against sepsis via modulating the oxidative stress parameters concomitant with the suppression of inflammatory reactions such as PGE2 and COX-2.

Chemotherapeutic effect of Berberis integerrima hydroalcoholic extract on colon cancer development in the 1,2-dimethyl hydrazine rat model.

The aim of this study was to investigate the efficacy of a Berberis integerrima hydroalcoholic extract as a chemotherapeutic agent in colon carcinogenesis in the rat induced by 1,2-dimethyl hydrazine (DMH). Male Wistar rats were divided into five groups: a negative control group without DMH treatment; a control group injected DMH (20 mg/kg b.w); two groups receiving B. integerrima extract (50 and 100 mg/kg b.w), concomitant with injected DMH, as chemotherapeutic groups; a positive control group receiving 5-fluorouracil (5-FU) along with DMH. The effects of the extracts were determined by assessment of hepatic malondialdehyde (MDA), glutathione (GSH), ferric reducing ability of plasma (FRAP), and the activities of hepatic glutathione S-transferase and cytochrome P450 (GST and CYP450). Additionally, colon tissues were assessed for colonic ß-catenin and histopathological analysis. In DMH-treated rats, the extracts partially normalized the levels of FRAP, CYP450, ß-catenin, and GST. Likewise, formation of aberrant crypt foci (ACF) in colon tissue of DMH-treated was reduced by the extracts. Thus, the extracts possess chemotherapeutic activity against colon carcinogenesis.

Hepatoprotective effects of Iranian Hypericum scabrum essential oils against oxidative stress induced by acetaminophen in rats

This studied examined the protective role of Hypericum scabrum oils (100 and 200 mg/kg b.w, i.p) on acetaminophen-induced liver damages in the rat. The hepatic oxidative/antioxidant parameters such as lipid peroxidation (LP), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and ferric reducing ability of plasma (FRAP) were measured 2, 4, 8, 16 and 24h after the treatments confirmed by histopathological consideration. The results indicated that increased levels of hepatic LP and FRAP and SOD activity were reversed in the rats treated with oils. In addition, the depleted GSH were compensated with the oil treatments. The protective effect of the oils was further confirmed by the histophatological examination carried out on liver biopsies. The data pointed out that H. scabrum oil could modulate the hepatic toxicity induced by the APAP through adjusting the oxidative stress/antioxidant parameters and could be of potential candidate for the treatment of acetaminophen induced oxidative stress liver damages.

Potential preventive role of Iranian Achillea wilhelmsii C. Koch essential oils in acetaminophen-induced hepatotoxicity.

BACKGROUND: The essential oil of Achillea wilhelmsii C. Koch (100 & 200 mg/kg b.w, i.p) was evaluated against acetaminophen induced hepatic injuries in rats. For this purpose, the activities of cytochrome P450 (CYP450), glutathione s-transferase (GST) and markers of liver injuries (ALT, AST, ALP) together with level of GSH measured analytically in time intervals (2, 4, 8, 16 & 24 h) after treatments confirmed by histophatological consideration in rat livers. RESULTS: Administration of acetaminophen (500 mg/kg bw, i.p) significantly increased the activity of CYP450 concomitant with increasing the release of ALT and AST. Whereas, GSH level and GST activity were decreased significantly after acetaminophen treatment. Treatment of rats with Achillea wilhelmsii essential oils significantly modulate these parameters to normal values. Also, histophatological analysis of liver biopsies was consistent with the biochemical findings. CONCLUSION: The data led us to conclude the curative potential of Achillea wilhelmsii essential oils against APAP induced hepatic injuries.

Effect of dietary caraway essential oils on expression of ß-catenin during 1,2-dimethylhydrazine-induced colonic carcinogenesis.

We have recently reported that the inhibition of colonic premalignant lesions induced by 1,2-dimethylhydrazine (DMH) is mediated by the interference of caraway oil components in the activities of the main hepatic xenobiotic metabolizing enzymes. The present study was carried out to examine the effect of dietary caraway oils on the progression of cancer, with emphasis on ß-catenin expression in the colon during DMH-induced colonic carcinogenesis. For this purpose, colon cancer was induced by DMH in rats (20 mg/kg body weight for 5 weeks) and groups of animals were given dietary caraway essential oils at two levels (0.01 and 0.1%) for 16 weeks. After 16 weeks and at the end of the experimental period the colon tissue biopsies were processed for histopathological examination and the expression of ß-catenin at mRNA and protein levels was estimated by polymerase chain reaction and enzyme-linked immunosorbent assay. The formation of premalignant lesions based on aberrant crypt foci (ACF) in DMH-treated rats was greatly inhibited (72-87%) in rats given dietary essential oils when compared to respective controls. There was a correlation between the number of colonic ACF formation and the expression levels of ß-catenin measured at protein and mRNA levels. These results indicate that the Wnt/ß-catenin signaling pathway is activated during colon cancer promotion and that the expression of colonic ß-catenin is altered in long-term caraway oil feeding, leading to suppression of DMH-induced premalignant lesions in rat colon.

Heart and kidney oxidative stress status in septic rats treated with caraway extracts.

CONTEXT: Carum carvi L., (Umbelliferae) known as caraway, is a famous traditional herbal plant supposed to contain active components with pharmacological properties. OBJECTIVE: In this study, the effects of caraway extracts on preventing sepsis induced by oxidative tissue injuries have been investigated by measuring heart and kidney oxidative stress parameters. MATERIALS AND METHODS: Sepsis was induced in rats (n = 6) by experimental cecal ligation and puncture (CLP) model. Then, either hydroalcoholic extract or essential oils (50 and 100 mg/kg body weight) were injected intraperitonially immediately after CLP operation. Twenty-four hours after CLP, the rats were anesthetized when kidney and heart tissues were removed to analyze the tissue oxidative stress parameters, that is, glutathione (GSH) and lipid peroxidation (LP). RESULTS: Sepsis induction caused a significant increase in kidney but not heart LP, indicating that kidney was more affected by sepsis induction than heart. Kidney LP and plasma urea/creatinine ratio levels were readily reversed in rats treated with essential oils but not in those treated with hydroalcoholic extract. Unlike LP, the heart and kidney GSH levels were not affected in all treated groups. DISCUSSION AND CONCLUSION: Our data imply that caraway oils probably have a protective role in kidney tissue against oxidative injury in advanced stages of sepsis.

Changes in hepatic cytosolic glutathione S-transferase activity and expression of its class-P during prenatal and postnatal period in rats treated with aflatoxin B1.

The effect of aflatoxin B1 (AFB1) on the expression of glutathione S-transferase-P (GST-P) which is the major isoform of GST in developmental stages has been investigated in rat liver during prenatal and postnatal stages. Following administration of AFB1 (0, 0.5, 1.0, 2.0, 3.0 or 4.0 mg/kg bw) injected I.P on day 8.5 of gestation the number of dead or reabsorbed fetuses and malformed embryos were recorded. Then the fetal livers were processed for measurement of total GST and GST-P activities, using 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid (ETA) as substrates respectively. RT-PCR using rat GST-P specific primers was performed on mRNA extracted from livers. Besides, the effects of AFB1 on hepatic GST and GST-P were assessed in groups of suckling rats directly injected with the toxin. The results show that a single dose of AFB1 (1.0 or 2.0 mg/kg bw) caused approximately 50-60% depletion in fetal liver GST towards CDNB. Postnatal experiments revealed that liver GST (using CDNB as substrate) was significantly induced (approximately 40%) in suckling rats injected with a single dose of AFB1 (3.0 mg AFB1/kg) 24 h before killing. Liver GST-P expression was unaffected due to AFB1 exposures of rats before and after the birth. This finding was substantiated by western blotting and RT-PCR techniques. These data suggest that AFB1-related induction in rat liver total GST after birth may be implicated in protective mechanisms against AFB1. In contrast, inhibition of this enzyme in fetal liver following placental transfer of the carcinogen may explain high susceptibility of fetal cells to trans-plancental aflatoxins. Furthermore, lack of influence of AFB1 on GST-P expression in developmental stages can role out the involvement of this class of GST in AFB1 biotransformation.

Differential effects of acetaminophen on enzymatic and non-enzymatic antioxidant factors and plasma total antioxidant capacity in developing and adult rats.

Recently we reported that ferric reducing ability of plasma (FRAP) assay, as an index of total antioxidant activity, increases in growing rats in response to high dose of vitamin K. In this study, it was found that acetaminophen (APAP) can cause elevation in FRAP in suckling and adult rats. This study was initiated to assess the contribution of individual antioxidant factors on elevation in FRAP. A surge in FRAP, 1 h after high dose APAP (250 or 450 mg/kg BW) administration was recorded in both young as well as adults. Whereas, low dose drug (25 mg/kg) failed to alter FRAP in both the age groups. Time-course studies show that drug-dependent elevation in FRAP begin rapidly, reaching a maximum at 1 h (> 500%). Increased FRAP was associated with a marked increase (approximately 14-fold) in plasma bilirubin, 6 h after drug administration at 450 mg/kg only in suckling rats. Similarly, APAP-related increase in superoxide dismutase activity in erythrocytes was limited to young rats of both the age groups. Other factors measured during this period viz., plasma uric acid, bilirubin and total protein together with catalase activity of erythrocytes remained unchanged in treated rats. Under these circumstances, APAP-related depletion in liver glutathione was almost similar in both the age groups. During a 12 h study, the concentration of lipid peroxidation products, in liver of treated groups remained within the levels of respective controls. The endpoint hepatotoxic effects of APAP was almost similar in both the age groups, suggesting that like adults, immature rats can cope with toxic effects of APAP owing to their drug-dependent induction in certain antioxidant factors.