The Protective Effect of Green Tea Extract on Alpha-amanitin Induced Hepatotoxicity

PURPOSE@#Alpha-amanitin induces potent oxidative stress and apoptosis, and may play a significant role in the pathogenesis of hepatotoxicity. This study examined the mechanisms of α-amanitin-induced apoptosis in vitro, and whether green tea extract (GTE) offers protection against hepatic damage caused by α-amanitin (AMA) induced apoptosis in vivo.@*METHODS@#The effects of GTE and SIL on the cell viability of cultured murine hepatocytes induced by AMA were evaluated using an MTT assay. Apoptosis was assessed by an analysis of DNA fragmentation and caspase-3. In the in vivo protocol, mice were divided into the following four groups: control group (0.9% saline injection), AMA group (α-amanitin 0.6 mg/kg), AMA+SIL group (α-amanitin and silibinin 50 mg/kg), and AMA+GTE group (α-amanitin and green tea extract 25 mg/kg). After 48 hours of treatment, the hepatic aminotransferase and the extent of hepatonecrosis of each subject was evaluated.@*RESULTS@#In the hepatocytes exposed to AMA and the tested antidotes, the cell viability was significantly lower than the AMA only group. An analysis of DNA fragmentation showed distinctive cleavage of hepatocyte nuclear DNA in the cells exposed to AMA. In addition, the AMA and GTE or SIL groups showed more relief of the cleavage of the nuclear DNA ladder. Similarly, values of caspase-3 in the AMA+GTE and AMA+SIL groups were significantly lower than in the AMA group. The serum AST and ALT levels were significantly higher in the AMA group than in the control and significantly lower in the AMA+GTE group. In addition, AMA+GTE induced a significant decrease in hepatonecrosis compared to the controls when a histologic grading scale was used.@*CONCLUSION@#GTE is effective against AMA-induced hepatotoxicity with its apoptosis regulatory properties under in vitro and in vivo conditions.

The Effect of Glehnia Littoralis on Alpha-amanitin Induced Hepatotoxicity in a Murine Model

PURPOSE: Glehnia littoralis has been reported to have several pharmacological properties but no in vivo reports describing the protective effects of this plant on α-amanitin-induced hepatotoxicity have been published. α-Amanitin is a peptide found in several mushroom species that accounts for the majority of severe mushroom poisonings leading to severe hepatonecrosis. In our previous in vitro study, we found that α-amanitin induced oxidative stress, which may contribute to its severe hepatotoxicity. The aim of this study was to investigate whether Glehnia littoralis acetate extract (GLEA) has protective antioxidant effects on α-amanitin-induced hepatotoxicity in a murine model. METHODS: Swiss mice (n=40 in all groups) were divided into four groups (n=10/group). Three hours after giving α-amanitin (0.6 mg/kg, i.p.) to the mice, they were administered silibinin (50 mg/kg/d, i.p.) or Glehnia littoralis ethyl acetate extract (100 mg/kg/d, oral) therapies once a day for 3 days. After 72 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurement, and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was assessed by a pathologist blinded to the treatment group and divided into 4 categories according to the grade of hepatonecrosis. RESULTS: GLEA significantly improved the beneficial functional parameters in α-amanitin-induced hepatotoxicity. In the histopathological evaluation, the toxicity that was generated with α-amanitin was significantly reduced by GLEA, showing a possible hepatoprotective effect. CONCLUSION: In this murine model, Glehnia littoralis was effective in limiting hepatic injury after α-amanitin poisoning. Increases of aminotransferases and degrees of hepatonecrosis were attenuated by this antidotal therapy.

In vitro Protective Effects of Glehnia Littoralis on Alpha-amanitin Induced Hepatotoxicity

PURPOSE: Glehnia littoralis has been used to treat ischemic stroke, phlegm, cough, systemic paralysis, antipyretics and neuralgia. The pharmacological mechanisms of Glehnia littoralis include calcium channel block, coumarin derivatives, anticoagulation, anti-convulsive effect, as well as anti-oxidant and anti-inflammatory effects. Alpha-amanitin (α-amanitin) is a major toxin from extremely poisonous Amanita fungi. Oxidative stress, which may contribute to severe hepatotoxicity was induced by α-amanitin. The aim of this study was to investigate whether Glehnia littoralis ethyl acetate extract (GLEA) has the protective antioxidant effects on α-amanitin -induced hepatotoxicity. METHODS: Human hepatoma cell line HepG2 cells were pretreated in the presence or absence of GLEA (50, 100 and 200µg/ml) for 4 hours, then exposed to 60µmol/L of α-amanitin for an additional 4 hours. Cell viability was evaluated using the MTT method. AST, ALT, and LDH production in a culture medium and intracellular MDA, GSH, and SOD levels were determined. RESULTS: GLEA (50, 100 and 200µg/ml) significantly increased the relative cell viability by 7.11, 9.87, and 14.39%, respectively, and reduced the level of ALT by 10.39%, 34.27%, and 52.14%, AST by 9.89%, 15.16%, and 32.84%, as well as LDH by 15.86%, 22.98%, and 24.32% in culture medium, respectively. GLEA could also remarkably decrease the level of MDA and increase the content of GSH and SOD in the HepG2 cells. CONCLUSION: In the in vitro model, Glehnia littoralis was effective in limiting hepatic injury after α-amanitin poisoning. Its antioxidant effect is attenuated by antidotal therapy.

Effects of Paraquat Ban on Herbicide Poisoning-Related Mortality

PURPOSE: In Korea, registration of paraquat-containing herbicides was canceled in November 2011, and sales thereof were completely banned in November 2012. We evaluated the effect of the paraquat ban on the epidemiology and mortality of herbicide-induced poisoning. MATERIALS AND METHODS: This retrospective study analyzed patients treated for herbicide poisoning at 17 emergency departments in South Korea between January 2010 and December 2014. The overall and paraquat mortality rates were compared pre- and post-ban. Factors associated with herbicide mortality were evaluated using logistic analysis. To determine if there were any changes in the mortality rates before and after the paraquat sales ban and the time point of any such significant changes in mortality, R software, version 3.0.3 (package, bcp) was used to perform a Bayesian change point analysis. RESULTS: We enrolled 2257 patients treated for herbicide poisoning (paraquat=46.8%). The overall and paraquat poisoning mortality rates were 40.6% and 73.0%, respectively. The decreased paraquat poisoning mortality rate (before, 75% vs. after, 67%, p=0.014) might be associated with increased intentionality. The multivariable logistic analysis revealed the paraquat ban as an independent predictor that decreased herbicide poisoning mortality (p=0.035). There were two major change points in herbicide mortality rates, approximately 3 months after the initial paraquat ban and 1 year after complete sales ban. CONCLUSION: This study suggests that the paraquat ban decreased intentional herbicide ingestion and contributed to lowering herbicide poisoning-associated mortality. The change point analysis suggests a certain timeframe was required for the manifestation of regulatory measures outcomes.

A Case of Methomyl-induced Acute Allergic Tubulointerstitial Nephritis

Drug-induced interstitial nephritis is one of the causes of acute kidney injury. Although methomyl is widely used as an insecticide in many countries, methomyl-induced interstitial nephritis has not been reported thus far in the general population. We report a case of a 39-year-old male patient with acute allergic tubulointerstitial nephritis due to methomyl intoxication. He took methomyl 250 mL to commit suicide. He was treated with hemodialysis, but his renal function continued to deteriorate. Kidney biopsy demonstrated mononuclear cell and some eosinophils infiltration into the renal interstitium with tubular invasion. Immediate steroid pulse therapy, appropriate education, and conservative management resulted in gradual restoration of his renal function. This case suggests that methomyl may be a causative allergen inducing acute interstitial nephritis in some patients.

A Clinical Analysis of Revision Endoscopic Sinus Surgery: Single-Center 10-Year Experience

BACKGROUND AND OBJECTIVES: Endoscopic sinus surgery (ESS) has become a popular procedure for treating chronic sinusitis. Despite recent developments in medical and surgical techniques, primary ESS can still fail. Although revision ESS is one solution to the problem of recurrent sinusitis, revision surgery is stressful for patients and otolaryngologists. Therefore, we examined the causes of ESS failure and sought to find ways to prevent the failure of primary ESS. MATERIALS AND METHODS: All patients who underwent revision ESS in our department between April 2003 and March 2012 were studied retrospectively. RESULTS: During this period, revision ESS was performed 40 times to treat chronic sinusitis. We analyzed the preoperative computed tomographic (CT) findings of primary and revision ESS cases using the Lund-Mackay and Kennedy CT staging scores to compare disease severity. In our cases, the failure of ESS was not affected by the extent of disease, asthma, or allergy. Polyposis was the only useful predictor of revision ESS. CONCLUSION: Polyposis is an important predictor of revision ESS. We recommend that patients be followed frequently and carefully, especially those with polyps.

Two Cases of Rhino-orbito-cerebral Mucormycosis / 대한이비인후과학회지

Mucormycosis is an acute, fatal infection caused by fungi of the family mucoraceae. The disease invariably occurs in diabetics, usually with ketoacidosis or immunocompromised patients. Typical initial symptoms of a patient with rhinocerebral mucormycosis are facial pain and swelling, headache, fever, and blood-tinged rhinorrhea. Symptoms rapidly progress to facial or orbital cellulitis, proptosis, and visual loss. Patients often may have infraorbital numbness, corneal anesthesia and facial nerve palsy. Recently, we experienced two cases of rhino-orbito-cerebral mucormycosis with atypical initial presentations. One case is a 54-year-old male, who had suddenly developed left facial palsy and periorbital swelling. The other is a 61-year-old female, who had right periorbital painful swelling with visual loss for 1 day. Herein we report the clinical courses and symptoms of these patients with literature review. Initial symptoms in making early diagnosis of rhino-orbito-cerebral mucormycosis are emphasized.