Srinivasan Periasamy

17β-Estradiol protects against acetaminophen-overdose-induced acute oxidative hepatic damage and increases the survival rate in mice

Acetaminophen overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of 17β-estradiol against acetaminophen-induced acute liver injury and mortality in mice. Male mice were given acetaminophen (p-acetamidophenol; 300 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased the levels of aspartate transaminase, alanine transaminase, myeloperoxidase, lipid peroxidation, and glutathione reductase, but it decreased superoxide dismutase, catalase, and glutathione. In addition, acetaminophen-induced mortality began 4h post-treatment, and all mice died within 9h. 17β-Estradiol (200 μg/kg; i.p.) protected against acetaminophen-induced oxidative hepatic damage by inhibiting neutrophil infiltration and stimulating the antioxidant defense system. However, 17β-estradiol did not affect acetaminophen-induced glutathione depletion or increased glutathione reductase activity. We conclude that 17β-estradiol specifically attenuates acute hepatic damage and decreases mortality in acetaminophen-overdosed male mice.

Sesame oil prevents acute kidney injury induced by the synergistic action of aminoglycoside and iodinated contrast in rats

ABSTRACT The aim of the study was to investigate the effect of sesame oil on acute kidney injury induced by the synergistic action of aminoglycoside and iodinated contrast in rats. Acute kidney injury was induced by a 5-day course of daily gentamicin injections (100 mg/kg of body weight, subcutaneously) and then iodinated contrast (4 ml/kg, intravenously) in male specific-pathogen-free Sprague-Dawley rats. Sesame oil (0.5 ml/kg, orally) was given 1 h before iodinated contrast. Renal function and oxidative stress were assessed 6 h after iodinated contrast injection. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels. Renal oxidative stress was assessed by determining renal lipid peroxidation, myeloperoxidase, hydroxyl radical, superoxide anion, nitrite/nitrate, and inducible nitric oxide synthase levels. Sesame oil significantly prevented the rise of serum blood urea nitrogen and creatinine levels. Furthermore, there was a parallel inhibition of the rise in levels of expression of renal lipid peroxidation, myeloperoxidase, hydroxyl radicals, superoxide anion, nitrite/nitrate, and inducible nitric oxide synthase in rats with gentamicin-plus-iodinated contrast-induced acute kidney injury. We conclude that sesame oil may attenuate aminoglycoside-plus-iodinated contrast-induced acute kidney injury by inhibiting renal oxidative stress in rats.

Sesame oil attenuates nutritional fibrosing steatohepatitis by modulating matrix metalloproteinases-2, 9 and PPAR-γ

Sesame oil is a nutrient-rich antioxidant popular in alternative medicine. It contains sesamin, sesamol, and sesamolin, all of which contribute to its improved liver function in various animal model studies. However, its effect on nutritional fibrosing steatohepatitis is unclear. We investigated therapeutic sesame oil on matrix metalloproteinases-2, 9 (MMP-2, 9) in nutritional fibrosing steatohepatitic mice. C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 35 days to induce fibrosing steatohepatitis. Sesame oil was treated from 29-35th day. Body weight, steatosis, aspartate transaminase, alanine transaminase, peroxisome proliferator-activated receptor (PPAR)-γ, α-smooth muscle actin (α-SMA), MMP-2, 9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were assessed after 35 days. All tested parameters except TIMP-1 and PPAR-γ were higher in MCD fed mice than in normal control mice. Mice fed with MCD diet for 4 weeks showed severe liver injury with steatosis, necrotic-inflammation, and fibrosis. In sesame-oil (4 ml)-treated mice, all tested parameters except TIMP-1, α-SMA, and PPAR-γ were significantly attenuated compared with MCD fed mice. Sesame oil inhibited MMP-2, 9 activities, but up-regulated TIMP-1 expression in MCD fed mice. In addition, a histological analysis of liver tissue samples showed that sesame oil provided significant protection against fibrosis. We conclude that therapeutic sesame oil protects against fibrosing steatohepatitis by inhibiting MMP-2, 9 activities, up-regulating TIMP-1 expression, and PPAR-γ.

Sesame oil mitigates nutritional steatohepatitis via attenuation of oxidative stress and inflammation: a tale of two-hit hypothesis

Nonalcoholic fatty liver disease, the most common chronic liver disorder worldwide, comprises conditions from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is associated with an increased risk of hepatocellular carcinoma. Sesame oil, a healthful food, increases resistance to oxidative stress, inflammation and protects against multiple organ injury in various animal models. We investigated the protective effect of sesame oil against nutritional steatohepatitis in mice. C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 28 days to induce NASH. Sesame oil (1 and 2 ml/kg) was treated from 22nd to 28th day. Body weight, steatosis, triglycerides, aspartate transaminase, alanine transaminase, nitric oxide, malondialdehyde, tumor necrosis factor-α, interlukin-6, interleukin-1β, leptin, and transforming growth factor-β1 (TGF-β1) were assessed after 28 days. All tested parameters were higher in MCD-fed mice than in normal control mice. Mice fed with MCD diet for 4 weeks showed severe liver injury with steatosis, oxidative stress, and necrotic inflammation. In sesame-oil-treated mice, all tested parameters were significantly attenuated compared with MCD-alone mice. Sesame oil inhibited oxidative stress, inflammatory cytokines, leptin, and TGF-β1 in MCD-fed mice. In addition, histological analysis showed that sesame oil provided significant protection against fibrotic collagen. We conclude that sesame oil protects against steatohepatitic fibrosis by decreasing oxidative stress, inflammatory cytokines, leptin and TGF-β1.

Sesame Oil Accelerates Healing of 2,4,6-Trinitrobenzenesulfonic Acid–Induced Acute Colitis by Attenuating Inflammation and Fibrosis

BACKGROUND Sesame oil is a component of traditional health food in Asian countries. Acute colitis is a form of inflammatory bowel disease (IBD) with chronic inflammatory disorder of the bowel. The precise etiology of IBD remains unknown, but it is believed that an abnormal host response to endogenous antigens causes initial tissue injury with amplification of the immune response. We investigated the protective effect of sesame oil against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in rats. METHODS Rats were intracolonically instilled with TNBS (120 mg/kg) using a cannula to induce colitis and then orally gavaged with sesame oil (4 mL/kg for 7 days) to attenuate TNBS-induced acute colitis. The acute colitis activity index (ACAI) was assessed using the colon weight/length ratio (mg/cm), thickness, extension of lesion, diarrhea, and macroscopic and microscopic damage scores. In addition, the degree of inflammation, mucins, and fibrosis was assessed by measuring mast cells, CD68(+) cells, neutral mucin, acidic mucin, collagen, and laminin on day 8 after inducing acute colitis. RESULTS All tested parameters except neutral mucins were significantly higher in TNBS-induced acute colitis. Sesame oil significantly decreased the degree of inflammation, fibrosis, and acidic mucin and increased neutral mucin. CONCLUSION We conclude that sesame oil accelerates the healing of an inflamed colon by inhibiting inflammation, acidic mucin, and fibrosis in TNBS-induced acute colitis in rats.

Sesame Oil Attenuates Ovalbumin-Induced Pulmonary Edema and Bronchial Neutrophilic Inflammation in Mice

Background. Allergic asthma is one of the most common chronic inflammatory diseases of airways. Severe asthma may lead to hospitalization and death. Sesame oil is a natural product with anti-inflammatory property. However, the effect of sesame oil on allergic asthma has never been studied. Objective. We investigate the effect of sesame oil on pulmonary inflammation in allergic asthma model. Methods. Allergic airway inflammation was induced by sensitizing with two doses of 10 mg ovalbumin (OVA) and then challenged with 1% OVA nebulizer exposure (1 h/day) for 3 days. Sesame oil (0.25, 0.5, or 1 mL/kg/day) was given orally 30 min before each challenge. Samples were collected 24 h after the last challenge. Results. Data showed that sesame oil inhibited pulmonary edema and decreased interleukin (IL)-1β and IL-6 levels in bronchoalveolar lavage fluid in OVA-treated mice. Sesame oil also decreased pulmonary nitrite level, inducible nitric oxide synthase expression, and neutrophil infiltration induced by OVA. Further, sesame oil decreased serum IgE level in OVA-treated mice. Conclusion. Sesame oil may attenuate pulmonary edema and bronchial neutrophilic inflammation by inhibiting systemic IgE level in allergic asthma.

Prophylactic Sesame Oil Attenuates Sinusoidal Obstruction Syndrome by Inhibiting Matrix Metalloproteinase–9 and Oxidative Stress

BACKGROUND Sinusoidal obstruction syndrome (SOS) occurs in patients undergoing hematopoietic cell transplantation and chemotherapy. The chemotherapeutic drugs oxaliplatin and cyclophosphamide cause SOS. Sesame oil is a nutrient-rich antioxidant popular in alternative medicine. It contains sesamin, sesamol, and sesamolin, all of which contribute to its antioxidant property. The authors investigated the protective effect of prophylactic sesame oil against monocrotaline-induced SOS in rats. METHODS Male Sprague-Dawley rats were gavaged with a single dose of sesame oil (0.5, 1, 2, or 4 mL/kg). One hour later, those rats were gavaged with monocrotaline (90 mg/kg) to induce SOS. Control rats were treated with saline only. Aspartate transaminase, alanine transaminase, laminin, collagen, myeloperoxidase, nitrate content, lipid peroxidation, glutathione levels, matrix metalloproteinase (MMP)-9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were assessed 48 hours after the monocrotaline gavage. RESULTS All tested parameters except TIMP-1, laminin, collagen, and glutathione were higher in monocrotaline-treated rats than in saline-only-treated control rats. In sesame oil-treated rats, all tested parameters except TIMP-1, laminin, collagen, and glutathione were significantly attenuated compared with monocrotaline-only-treated rats. Sesame oil downregulated MMP-9 expression but upregulated TIMP-1 expression in monocrotaline-only-treated rats. In addition, a histological analysis of liver tissue samples showed that sesame oil showed significant protection. CONCLUSION A single prophylactic dose of sesame oil protects against SOS by downregulating MMP-9 expression, upregulating TIMP-1 expression, and inhibiting oxidative stress.

Protective Effect of 3,4-Methylenedioxyphenol (Sesamol) on Stress-Related Mucosal Disease in Rats

Stress-related mucosal disease (SRMD) causes considerable morbidity and mortality in critically ill patients. 3,4-Methylenedioxyphenol (sesamol) has been reported to have potent antioxidative and anti-inflammatory properties. The aim of this study was to investigate the effect of sesamol on water immersion restraint- (WIR-) induced SRMD in rats. Rat gastric ulcer and hemorrhage were induced by WIR. Rats were pretreated orally with various doses of sesamol (0.1, 0.3, and 1 mg/kg, resp.) 30 min before WIR. Gastric mucosal ulceration, hemoglobin, lipid peroxidation, mucus secretion, proinflammatory cytokines, and nuclear factor (NF)-κB levels were determined 4 h after WIR. In addition, the infiltration of neutrophil and macrophage into gastric mucosa was also determined after WIR. Water immersion restraint increased gastric mucosal ulcer and hemorrhage, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels but failed to affect mucosal lipid peroxidation and mucus secretion compared with non-WIR. Sesamol significantly decreased gastric ulceration and hemorrhage and inhibited mucosal TNF-α, IL-1β, and IL-6 production and NF-κB activity in WIR-treated rats. In addition, increased myeloperoxidase and CD68 levels in gastric mucosa were found in WIR-treated rats compared to non-WIR rats. Sesamol did not affect myeloperoxidase but decreased CD68 levels in mucosa in WIR-treated rats. Sesamol may protect against SRMD by inhibiting gastric mucosal proinflammatory cytokines in rats.

Sesamol attenuates isoproterenol-induced acute myocardial infarction via inhibition of matrix metalloproteinase-2 and -9 expression in rats

Background/Aims: The protective role of sesamol and its possible action against isoproterenol-induced myocardial injury and infarction is unknown. We tested the hypothesis that sesamol’s protection against myocardial infarction is associated with the inhibition of matrix metalloproteinase (MMP)-2 and MMP-9. Methods: Four groups of experimental rats were subcutaneously injected with sesamol (0, 1, 3, or 10 mg/kg) and then, 2 h later, intraperitoneally injected with isoproterenol (100 mg/kg 24 h apart on 2 consecutive days) to induce myocardial infarction. Control rats were treated with saline only. Blood pressure (BP), heart rate (HR), and electrocardiography (ECG) wave durations, serum creatine phosphokinase isoenzymes (CKMB), lactate dehydrogenase (LDH), myocardial histology, MMP-2, and MMP-9 were assessed 24 h after the last dose of isoproterenol was given. Results: BP was lower, and HR, ECG wave durations, CKMB, LDH, myocardial injury, MMP-2, and MMP-9 levels were higher in experimental rats than in control rats. BP was significantly higher, and all the other parameters were significantly lower in the rats treated with sesamol than in those treated with isoproterenol only. Conclusions: Sesamol effectively prevented myocardial infarction, at least in part, by controlling proteolytic activities and the expression of MMP-2 and -9 in isoproterenol-treated rats.

Sesame oil accelerates kidney healing following gentamicin-induced kidney injury in rats.

Background/Aims:We investigated the therapeutic effect of a single dose of sesame oil against gentamicin-induced renal damage in rats. Methods: Experimental rats were subcutaneously injected with gentamicin (100 mg/kg/day for 7 days) to induce renal injury. Sesame oil (1, 2 or 4 ml/kg) was given orally 24 h after the last dose of gentamicin. Control rats were treated with saline only. Renal injury, histopathological examination, histochemical staining, osteopontin expression, superoxide anion, nitric oxide, peroxynitrite radical and lipid peroxidation were assessed 24 h after sesame oil administration. Results: Serum blood urea nitrogen and creatinine as well as renal osteopontin expression, superoxide anion, nitric oxide, peroxynitrite radical and lipid peroxidation levels were higher in gentamicin-treated rats than in control rats. Sesame oil significantly decreased all the tested parameters compared with gentamicin-alone rats. Furthermore, histopathological and histochemical staining showed that renal tubules had recovered and regenerated in the sesame oil-treated rats. Conclusion: We hypothesize that a single dose of sesame oil inhibits oxidative stress to shorten the recovery period and allow the regeneration of renal tubules after the onset of gentamicin-induced renal injury in rats.