• Toxicological Research
• /
• 제14권2호
• /
• pp.151-156
• /
• 1998

Acetaminophen (APAP) and gentamicin are widely used for many patients, but little in-formation is available regarding the combined effects of APAP and gentamicin. This study was aimed to investigate the potent nephrotoxicity following combined-treatment with APAP and gentamicin. Serum biochemical parameters and histopathological changes in the kidney were observed in female SD rats after continuous daily treatment with either 600 mg/kg/day APAP, and/or 300 mg/kg/day gentamicin for 3 days, and compared with saline sham-treated control animals. APAP and gentamicin combination-treated rats exhibited inconsistent increasing tendency in blood urea nitrogen (BUN) by 96 hours after the last treatment, compared to control or the animals treated with each drug. The relative kidney weights were also increased. Histopathological findings of kidneys revealed that necrosis of proximal convoluted tubules were higher in rats treated with APAP and gentamicin combination than the rats treated with each drug alone. These results suggest that combination use of both drugs have more severe nephrotoxicity than treating each drug alone.

• 한국환경보건학회:학술대회논문집
• /
• 한국환경보건학회 2005년도 가을학술대회
• /
• pp.169-174
• /
• 2005

의약품은 일반적으로 치료를 목적으로 제조되었기 때문에 독특한 약리학적 작용을 띤다. 의약품잔류물이 환경 중으로 배출되어 비표적 생물(non-target organism)에 노출될 경우 의도하지 않은 독성영향이 나타날 가능성이 있다. 본 연구에서는 우리나라에서 널리 사용되는 10개의 의약품(4종의 일반 의약품 acetaminophen, carbamazepine, diltiazem, cimetidine과 6종의 설파계 항생제 sulfamethoxazole, sulfamethazine, trimethoprim, sulfachloropyridazine, sulfadimethoxine)을 대상으로 환경중 예상잔류농도와 생태 무영향농도를 예측하여 대상의약품의 생태위해성을 평가하였다. 연구대상 의약품의 예측환경농도는 0.14 ${\sim}$ 16.5 ppb이었으며, 예측환경농도와 예측무영향농도비(PEC/PNEC ratio)를 산출한 결과 acetaminophen과 suifamethoxazole이 각각 1.8과 6.3으로 나타나 이 의약품들이 물생태계에 미치는 위해성에 대한 정밀한 추가연구의 필요성이 제시되었다.

• 한국환경성돌연변이발암원학회:학술대회논문집
• /
• 한국환경성돌연변이발암원학회 2004년도 KSOT/KEMS Fall Annual Meeting
• /
• pp.130-130
• /
• 2004

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 2000년도 춘계학술대회
• /
• pp.20-25
• /
• 2000

아세트아미노펜(파라세타몰)은 p-aminophenol 유도체로서 (그림 1) 두통, 치통, 신경통 등의 통증에 널리 사용되는 해열진통제인데 아스피린과 같은 정도의 해열 진통 효과를 나타내며, 이것은 중추신경계의 체온조절 중추에 작용하여 피부혈관을 확장함으로써 열의 확산을 증가시키는 해열작용과 시상 및 대뇌피질에의 통각역치를 높여 진통작용을 하는 것으로 추정 된다. 아세트아미노펜은 백색의 결정 또는 결성성 가루로 물에 조금 녹고 메탄올 또는 에탄올에 잘 녹으며 수산화나트륨 시액에 녹고 에텔에는 매우 녹기 어렵다 (표1). 대한약전에서는 정제가, 미국약전에는 캅셀제, 좌제, 경구현탁액제, 발포성 건조시럽, 정제 등이 수재되어 있고, 세계 각국에서 OTC 제품으로 1정당 160mg의 츄잉정까지 판매되고 있다. 그러나, 시판되고 있는 정제등은 붕해되어 용출되는데 오랜시간이 소요되어 대한약전에는 약 30분간에 80%이상의 용출기준이 설정되어 있으며, 독특한 쓴맛 때문에 microencapsulation 한 제피세립을 사용하고 있으나 역시 1 정당 300mg 이상의 확산정이나 속용정은 존재하지 않는다. 이것을 개선하기 위하여 붕해속도가 빠르고 특히 진통효과가 빠르며 물없이 구강내에서 간편히 녹여 복용하거나 또는 씹어서 또는 물과 함께 복용할 수 도 있는 $\ulcorner$알카펜$\lrcorner$ 속용정을 개발하게 되었다 (그림2).

• Biomolecules & Therapeutics
• /
• 제12권3호
• /
• pp.185-188
• /
• 2004

The purpose of this study is to evaluate the effect of cigarette smoke condensate (CSC) on toxification/detoxification metabolic pathway in primary cultured rat hepatocytes. We measured the activities of cytochrome P450 monooxygenases (CYP450s) and UDP-glucuronyltransferase, sulfotransferase and glutathione-S-transferase in CSC-treated rat hepatocytes. CSC significantly increased the activities of hepatic CYP4501A1 and CYP4501A2 to 7.5 fold and 1.6 fold respectively, compared with control level. However, CSC did not affect the activities of conjugation enzymes. We a1so examined if treatment of CSC could change thc cytotoxicity of acetaminophen (AA) through modulation of metabolizing enzymes. In rat hepatocytes, pretreatment with CSC potentiated the cytotoxicity of AA. This result indicates that potentiation of AA toxicity by CSC pretreatment may be related to induction of CYP4501A1 and CYP4501A2.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1995년도 춘계학술대회
• /
• pp.109-109
• /
• 1995

정상 동물군의 GOT값 및 GPT 값이 각각 137.8$\pm$23.4 및 67.4$\pm$10.0 이었고 acetaminophen 투여군은 418.6$\pm$69.1 및 447.4$\pm$7.7로 증가하였으나 G009 투여군은 그 증가가 현저히 억제되었다. 즉 G009 10mg/kg 투여군은 GOT 및 GPT 값이 192.6$\pm$19.2 및 144.8$\pm$28.7에 그쳐 각각 GOT 및 GPT 값의 상승이 80.5% 및 79.6% 억제되었고 20mg/kg 투여군은 90.8% 및 86.6% 억제되었다. 그러나 Licovek 은 50mg/kg의 투여군에서 이와 유사한 효과가 관찰되었다. 또한 간 절편의 조직학적 관찰 결과 acetaminophen 투여 대조군이 간세포 괴사등 심한 조직 괴사를 보인 반면 G009 10mg/kg 및 20mg/kg 농도에서는 간장 손상이 매우 경미함을 확인할 수 있었다.

• Journal of Pharmaceutical Investigation
• /
• 제21권4호
• /
• pp.201-213
• /
• 1991

There are many drugs reproted to show unusual pharmacokinetic behavior by producing a significant secondary peak in the plasma concentration-time curve after oral administration. The drugs are ranitidine, cimetidine, acetaminophen, aspirin, furosemide, bumetanide, piretanide, veralipride, sobrerol, penicillamine and doxycycline etc. Enterohepatic circulation-, two absorption site-, biphasic gastric emptying-, tissue deposition- and multi-fraction absorption theories have been suggested for the mechanisms of this phenomenon. Here, the theories were reviewed and critisized for their validity as a possible mechanism of the multiple peak phenomenon.

• 대한의생명과학회지
• /
• 제25권1호
• /
• pp.54-59
• /
• 2019

Hepatitis refers to inflammation of hepatocytes and liver tissue, and is mainly caused by viruses, alcohol, and drugs. Forsythiae Fructus has traditionally been used as a diuretic, anti-inflammatory and antipyretic. Research on rengyolone, a bioactive substance extracted from Forsythiae Fructus, is rarely found in Korea and abroad. First, an acute animal toxicity test for rengyolone was conducted for the animal experiment. 4 week-old SD rats were injected intraperitoneally with acetaminophen for 2 weeks to induce chronic liver inflammation. Rengyolone was orally administered into two groups during 4 weeks: pre-inflammatory group and post-inflammatory group. Oral doses were also divided into 1 mg/kg and 5 mg/kg. Liver function tests (ALT, AST, ALP), western blot analysis of liver tissue, and level of inflammatory cytokine were performed to evaluate the improvement of hepatitis. Experimental results showed that rengyolone inhibited the development of acute inflammation and thus could reduce hepatitis symptoms.

• Biomolecules & Therapeutics
• /
• 제17권4호
• /
• pp.455-460
• /
• 2009

Foods of plant origin, especially fruits and vegetables, have attracted attention because of their potential benefits to human health. In this report, Rubi Fructus (RF), the dried unripe fruit of Rubus coreanus Miq (Rosaceae) and ellagic acid (EA) purified from RF were used to test their potential hepatoprotective effect against acetaminophen (AAP)-induced hepatotoxicity in rats. RF extract (RFext) and EA reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum and the content of lipid peroxide in liver by AAP administration, while the increment of the cellular glutathione (GSH) content and the induction of glutathione S-transferase (GST) and glutathione peroxidase (GSH-PX) which were decreased by AAP administration. RFext and EA from RFext did not affect the two major form of cytochrome P450s, cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2), but downregulated the cytochrome P450 3A4 (CYP3A4) related to the conversion of AAP to N-acetyl-P-benzoquinone imine (NAPQI). These results suggest that RFext and EA from RF exhibit a hepatoprotective effect not only by increasing antioxidant activities but also by down-regulating CYP3A4 in the AAP-intoxicated rat.

• Biomolecules & Therapeutics
• /
• 제17권4호
• /
• pp.438-445
• /
• 2009

We investigated global gene expression from both mouse liver and mouse hepatic cell lines treated with acetaminophen (APAP) in order to compare in vivo and in vitro profiles and to assess the feasibility of the two systems. During our analyses of gene expression profiles, we picked up several down-regulated genes, such as the cytochrome P450 family 51 (Cyp51), sulfotransferase family cytosolic 1C member 2 (Sult1c2), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1), and several genes that were up-regulated by APAP, such as growth arrest and DNA-damage-inducible 45 alpha (Gadd45a), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1) and zinc finger protein 688 (Zfp688). For validation of gene function, synthesized short interfering RNAs (siRNAs) for these genes were transfected in a mouse hepatic cell line, BNL CL.2, for investigation of cell viability and mRNA expression level. We found that siRNA transfection of these genes induced down-regulation of respective mRNA expression and decreased cell viability. siRNA transfection for Cyp51 and others induced morphological alterations, such as membrane thickening and nuclear condensation. Taken together, siRNA transfection of these six genes decreased cell viability and induced alteration in cellular morphology, along with effective inhibition of respective mRNA, suggesting that these genes could be associated with APAP-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity, for better understanding of its mechanism.