Victor Raj Mohan Chandrasekaran

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 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.

Anti-hepatotoxic effects of 3,4-methylenedioxyphenol and N-acetylcysteine in acutely acetaminophen-overdosed mice.

3,4-Methylenedioxyphenol (sesamol) is effective against acetaminophen-induced liver injury in rats. Whether sesamol’s anti-hepatotoxic effect is comparable to that of N-acetylcysteine has never been studied. We investigated the anti-hepatotoxic effects of sesamol and N-acetylcysteine on acetaminophen-induced hepatotoxicity in mice. Equimolar doses (1 mmol/kg) of sesamol and N-acetylcysteine significantly inhibited acetaminophen (300 mg/kg)-increased serum aspartate transaminase and alanine transaminase levels 6 h post-administration. Sesamol and N-acetylcysteine maintained hepatic glutathione levels and inhibited lipid peroxidation. Moreover, the combination of sesamol and N-acetylcysteine antagonistically inhibited sesamol’s protection against acetaminophen-induced liver injury. We conclude that the protective effect of sesamol against acetaminophen-induced liver damage is comparable to that of N-acetylcysteine by maintaining glutathione levels and inhibiting lipid peroxidation in mice.

Using iron precipitants to remove arsenic from water: Is it safe?

Arsenic-associated health complications are reported worldwide. Arsenic is a documented toxic element in drinking water. Removing arsenic from drinking water is widely dependent on iron-based techniques. Although inorganic arsenic has long been known to be toxic to humans, little is known about the toxic effect of the interaction between arsenic and iron. We investigated the effect of arsenic plus iron on the liver of rats. We gave rats sodium arsenite, iron, or sodium arsenite plus iron. Neither the arsenic-alone nor the iron-alone treatments altered their serum aspartate or alanine transaminase levels. However, a combination of non-toxic doses of arsenite and iron synergistically increased serum aspartate and alanine transaminase levels and lipid peroxidation in liver tissue. Therefore, we hypothesize that arsenic plus iron synergistically induces hepatic damage mediated through oxidative stress in rats. Our study indicates an important public health issue: using iron precipitants to remove arsenic from water may cause oxidative hepatic damage in humans.

Role of flavin-containing-monooxygenase-dependent neutrophil activation in thioacetamide-induced hepatic inflammation in rats

Thioacetamide is widely used in industry and is known to be one of the most potent hepatotoxicants in experimental animals. We investigated the involvement of flavin-containing monooxygenase (FMO)-dependent hepatic-neutrophil activation and the release of proinflammatory mediators in thioacetamide-induced hepatic injury in rats. Thioacetamide (100 mg/kg, intraperitoneally) increased, within 12 h, hepatic serum aspartate transferase and alanine transferase levels, tumor necrosis factor-α production, interleukin-1β and nitrite levels, and myeloperoxidase activity. Rabbit anti-neutrophil serum markedly inhibited all thioacetamide-altered parameters. In addition, FMO-competitive inhibitor methimazole reduced thioacetamide-induced myeloperoxidase activity, hepatic tumor necrosis factor-α, interleukin-1β, nitrite, inducible nitric oxide synthase, and hepatic damage in thioacetamide-treated rats. Thus, we conclude that FMO-dependent hepatic neutrophil activation initiates the release of proinflammatory mediators in thioacetamide-treated rats.

Beneficial Effect of Sesame Oil on Heavy Metal Toxicity

Heavy metals become toxic when they are not metabolized by the body and accumulate in the soft tissue. Chelation therapy is mainly for the management of heavy metal-induced toxicity; however, it usually causes adverse effects or completely blocks the vital function of the particular metal chelated. Much attention has been paid to the development of chelating agents from natural sources to counteract lead- and iron-induced hepatic and renal damage. Sesame oil (a natural edible oil) and sesamol (an active antioxidant) are potently beneficial for treating lead- and iron-induced hepatic and renal toxicity and have no adverse effects. Sesame oil and sesamol significantly inhibit iron-induced lipid peroxidation by inhibiting the xanthine oxidase, nitric oxide, superoxide anion, and hydroxyl radical generation. In addition, sesame oil is a potent inhibitor of proinflammatory mediators, and it attenuates lead-induced hepatic damage by inhibiting nitric oxide, tumor necrosis factor-α, and interleukin-1β levels. Because metal chelating therapy is associated with adverse effects, treating heavy metal toxicity in addition with sesame oil and sesamol may be better alternatives. This review deals with the possible use and beneficial effects of sesame oil and sesamol during heavy metal toxicity treatment.

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.