Pei-Yi Chu

Attenuation of endotoxin-induced oxidative stress and multiple organ injury by 3,4-methylenedioxyphenol in rats

ABSTRACT Endotoxin is a potent inducer of lipid peroxidation (LPO), which is associated with the development of endotoxemia. 3,4-Methylenedioxyphenol (sesamol) is one of the sesame oil lignans with a high anti-LPO effect. Whether sesamol can attenuate endotoxin-induced LPO and multiple organ injury is unknown. After a dose response for sesamol in endotoxin-challenged rats was established, experiments were conducted to assess its effects on hydroxyl radical, peroxynitrite, and superoxide anion counts, activities of superoxide dismutase, catalase, and glutathione peroxidase, as well as the production of nitric oxide (NO) and the expression of inducible NO synthase. In addition, the effects of sesamol on endotoxin-induced hepatic and renal injuries were assessed. Sesamol (a) dose dependently reduced serum LPO inendotoxin-challenged rats, (b) decreased hydroxyl radical and peroxynitrite, but not superoxide anion counts, (c)increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in endotoxin-treated rats, (d)reduced NO production and inducible NO synthase expression, and (e) attenuated hepatic and renal injuries induced by endotoxin in rats. We concluded that sesamol might protect against organ injury by decreasing NO-associated LPO in endotoxemic rats.

Sesamol attenuates diclofenac-induced acute gastric mucosal injury via its cyclooxygenase-independent antioxidative effect in rats.

We examined the protective effects of sesamol against acute gastric mucosal damage induced in rats by nonsteroidal anti-inflammatory drug diclofenac (DLF). We also measured the ulcer index, nitrite, iNOS, lipid peroxidation, hydroxyl radical, superoxide anion, reduced glutathione levels, prostaglandin E2, mucus, and cyclooxygenase activity in the rat mucosa. Sesamol attenuated gastric ulcer, nitrite, and iNOS in DLF-treated stomachs. Sesamol reduced mucosal lipid peroxidation and hydroxyl radical levels; however, neither DLF nor sesamol affected mucosal superoxide anion production. In addition, sesamol significantly maintained the reduced mucosal glutathione levels in DLF-treated stomachs of rats. Sesamol did not affect mucosal mucus production, but it further decreased DLF-induced mucosal prostaglandin E2 generation and cyclooxygenase activity. Therefore, sesamol might protect gastric mucosa against DLF-induced injury by inhibiting hydroxyl radical-associated lipid peroxidation. In addition, the cyclooxygenase pathway may not be involved in sesamols gastric mucosal protection.

Effect of Sesame Oil on Acidified Ethanol-Induced Gastric Mucosal Injury in Rats

BACKGROUNDnExposure of gastric mucosa to concentrated ethanol induces acute gastritis. Gastric mucosal lipid peroxidation plays a significant role in the pathogenesis of ethanol-induced gastric mucosal lesions. The aim of this study was to investigate the effect of sesame oil on acidified ethanol-induced gastric mucosal damage in rats.nnnMETHODSnWe performed gastric bilateral vagotomy in rats. A small incision on forestomach was made and stomach content was expelled. Normal artificial gastric acid (54 mM NaCl plus 100 mM HCl) or acidified ethanol (30% ethanol plus 150 mM HCl) was instilled into the stomach. Gastric lipid peroxidation, glutathione, and nitric oxide levels were measured 3 hours after acidified ethanol administration.nnnRESULTSnAcidified ethanol caused mucosal ulceration, luminal hemorrhage, lipid peroxidation, and a lower level of mucosal glutathione and nitric oxide production. Pretreatment of sesame oil, but not mineral oil, significantly decreased acidified ethanol-induced mucosal ulcer formation and luminal hemorrhage. Sesame oil reduced mucosal lipid peroxidation, as well as glutathione and nitric oxide production in acidified ethanol-treated stomachs. Furthermore, both sesame oil and mineral oil did not affect serum ethanol concentration in acidified ethanol-treated rats.nnnCONCLUSIONnSesame oil attenuates acidified ethanol-induced gastric mucosal injury by reducing oxidative stress in rats.

Sesame oil protects against lead-plus-lipopolysaccharide-induced acute hepatic injury.

Lead (Pb) increases lipopolysaccharide (LPS)-induced tumor necrosis factor &agr;, which causes liver damage. In this study, we investigated the effect of sesame oil on Pb-plus-LPS (Pb + LPS)-induced acute liver damage in mice. Mice were given sesame oil (8 mL/kg orally) just after Pb acetate (10 mmol/kg i.p.) plus LPS (5 mg/kg i.p.). Aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor-&agr;, interleukin-1&bgr;, nitric oxide, and inducible nitric oxide synthase levels were examined. Sesame oil significantly decreased serum aspartate aminotransferase and alanine aminotransferase levels in Pb + LPS-stimulated mice. Sesame oil reduced Pb + LPS-induced tumor necrosis factor-&agr;, interleukin-1&bgr;, and nitric oxide production in serum and liver tissue. Furthermore, sesame oil decreased inducible nitric oxide synthase expression in leukocytes and liver tissue in Pb + LPS-treated mice. We hypothesize that the inhibition of proinflammatory cytokines and nitric oxide might be involved in sesame oil-associated protection against Pb + LPS-induced acute hepatic injury in mice.

Daily sesame oil supplement attenuates joint pain by inhibiting muscular oxidative stress in osteoarthritis rat model

Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the population. The aim of this study was to evaluate the efficacy of sesame oil in controlling OA pain in rats. Rat joint pain was induced by medial meniscal transection in Sprague-Dawley rats and assessed by using hindlimb weight distribution method. Muscular oxidative stress was assessed by determining lipid peroxidation, reactive oxygen species and circulating antioxidants. Sesame oil significantly decreased joint pain compared with positive control group in a dose-dependent manner. Sesame oil decreased lipid peroxidation in muscle but not in serum. Further, sesame oil significantly decreased muscular superoxide anion and peroxynitrite generations but increased muscular glutathione and glutathione peroxidase levels. Further, sesame oil significantly increased nuclear factor erythroid-2-related factor (Nrf2) expression compared with positive control group. We concluded that daily sesame oil supplement may attenuate early joint pain by inhibiting Nrf2-associated muscular oxidative stress in OA rat model.

The non-peptide chemical 3,4-methylenedioxyphenol blocked lipopolysaccharide (LPS) from binding to LPS-binding protein and inhibited pro-inflammatory cytokines

After binding to lipopolysaccharide (LPS)-binding protein, LPS is transferred to CD14 and then to the MD2—Toll-like receptor 4 complex, which results in the progression of sepsis. We investigated how 3,4-methylenedioxyphenol (sesamol), an inexpensive natural product in sesame seeds, affects the binding of LPS and LPS-binding protein and the release of pro-inflammatory cytokines. Sesamol: (i) dose-dependently inhibited LPS from binding to LPS binding protein; (ii) significantly decreased the release of tumor necrosis factor-α and interleukin-1β in LPS-challenged peritoneal macrophages in medium and in the serum of LPS-challenged rats; and (iii) significantly reduced the mortality rate in mice given a lethal dose of LPS. We hypothesize that sesamol blocks LPS from binding to LPS-binding protein and inhibits the release of pro-inflammatory cytokines, both of which are associated with a decrease of mortality in endotoxemia.

Enteral sesame oil therapeutically relieves disease severity in rat experimental osteoarthritis

Background Osteoarthritis (OA) is the most common cause of joint pain, affecting approximately 15% of the population. Recent studies indicate that quadriceps muscle weakness is directly involved in the pathogenesis of OA-associated joint pain. Oxidative stress plays an important role in skeletal muscle dysfunction. Sesame oil is a natural product with excellent antioxidative property. However, whether sesame oil can decrease OA-induced joint pain has never been investigated. Objective The aim of the present study was to examine the effect of sesame oil on OA-induced joint pain in rats. Design OA-associated joint pain in rats was induced by medial meniscal transection in rats. Sesame oil (0, 1, 2, or 4 ml/kg/day, orally) was given to rats 7 days after OA induction, while the parameters were determined 7 days after sesame oil administration. Results Daily sesame oil treatment for 7 days significantly decreased OA-associated joint pain. Sesame oil decreased muscular interleukin-6 and increased citrate synthase activity and myosin heavy chain IIa mRNA expression. Furthermore, sesame oil decreased muscular lipid peroxidation, nuclear Nrf2 protein expression, and reactive oxygen species generations as well as increased glutathione production and glutathione peroxidase activity in OA rats. Conclusions Sesame oil may relieve OA-associated joint pain by inhibiting quadriceps muscular oxidative stress, at least partially, in rats.

Exposure to acetamide-based compounds is a risk factor of acute hepatic inflammation

Introduction Acetamide-based compounds widely used in industries and their toxic effect have not been studied. Thioacetamide (TAA) is widely used in industry and is known to be a hepatotoxicants in experimental animals. However, the mechanism underlying TAA-induced acute inflammation is still unclear. The authors investigated the mechanisms and the involvement of main TAA metabolites in acute hepatic inflammation induced by TAA-in rats. Methods Acute hepatic inflammation was induced by TAA (0, 10, 30 and 100 mg/kg, intraperitoneally), while the inflammatory indicators including cytokines and nitric oxide were determined 0, 1, 3, 6 and 12 h after TAA administration. Hepatic pro-inflammatory cytokines were measured quantitatively using ELISA. SKF525A (cytochrome P450 2E1 (CYP 2E1) inhibitor) were used to examine the role of cytochrome in TAA-induced acute hepatic inflammation. In addition, TAA-S-oxide and acetamide were also used to examine the involvement of TAA metabolites in the early stage of TAA-induced hepatic inflammation. Results TAA increased, within 6 h, hepatic tumour necrosis factor-aproduction, interleukin 1b, nitrite levels, inducible nitric oxide synthase expression and myeloperoxidase activity. CYP 2E1 inhibitors showed significant inhibition of tumour necrosis factor α, interleukin 1β, nitrite, and myeloperoxidase activity after TAA treatment. In addition, acetamide, but not TAA-S-oxide, increased myeloperoxidase activity and all tested proinflammatory mediators generation. Conclusion The authors conclude that acetamide-associated neutrophil activation is involved, at least partially, in TAA-induced hepatic inflammation. Further, exposure to acetamide-based compounds may be a risk factor of acute hepatic inflammation.