AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.
AIMS To assess the protective effect of diallyl disulfide (DADS) and its combined use with N-acetyl-cysteine (NAC) on acetaminophen (APAP) hepatotoxicity in C57BL/6N (B6) mice pretreated with β naphthoflavone (BN...AIMS To assess the protective effect of diallyl disulfide (DADS) and its combined use with N-acetyl-cysteine (NAC) on acetaminophen (APAP) hepatotoxicity in C57BL/6N (B6) mice pretreated with β naphthoflavone (BNF). METHODS B6 mice were divided into six groups and all compounds used were injected intraperitoneally. Except for control and APAP group (receiving APAP only), the other groups received an injection of APAP (350mg/kg) 48 hours after BNF (200mg/kg) and either of DADS (200mg/kg), or NAC (500mg/kg) or both DADS and NAC. DADS was given 2 hours before APAP and NAC was injected with APAP. The mean survival time was recorded and livers were examined histologically. Hepatic glutathione (GSH) levels and plasma ALT were also determined at different time points. To evaluate the effect of DADS or NAC on hepatic P450 induction by BNF, liver microsomes were prepared and 7 ethoxyresorufin O dealkylase (ERD) activity was determined using spectrofluorometrical methods. In vitro effect of DADS or NAC on ERD activity was assayed by directly incubating microsomal suspension with DADS or NAC of different concentrations. RESULTS APAP was not toxic to mice without BNF pretreatment, but caused severe liver necrosis and death of all BNF treated mice in 4 hours. A sharp depletion of GSH (approximately 62% of its initial content at 2 hours and 67% at 4 hours) and a linear elevation of ALT levels (536 8±29 5 Sigma units at 2 hours and 1302 5±74 9 at 4 hours) were observed. DADS and NAC given individually produced mild protection, resulting in prolonged survival, a slower decline of GSH level and a less steeper elevation of ALT level. All mice died eventually. Co administration of DADS and NAC completely protected mice. GSH level in this group lowered by about 35% and 30% at 2 and 4 hours, and ALT was 126±18 and 157 5±36 6 Sigma units at 2 and 4 hours. ERD activity in BNF treated mice was about 5 times that of the constitutive level determined in normal mice. Neither DADS nor NAC inhibited P450 1A1/1A2 induction as determined by their effect on the induction of ERD activity. In vitro assay indicates that DADS, but not NAC, was a potent inhibitor of ERD activity (IC 50 =4 6μM). CONCLUSIONS A combined use of both DADS and NAC produced full protection in BNF treated mice against APAP hepatotoxicity. The mechanism is that DADS inhibits P450 1A1/1A2 activity, but not induction, which substantially reduces production of NAPQI, while NAC enhances liver detoxifying capability via serving as a precursor of GSH and stimulating GSH synthesis.展开更多
Specific, precise and sensitive TLC-Densitometric method was developed and validated for the simultaneous estimation of N-Acetyl cysteine and Taurine in active pharmaceutical ingredient and pharmaceutical dosage form....Specific, precise and sensitive TLC-Densitometric method was developed and validated for the simultaneous estimation of N-Acetyl cysteine and Taurine in active pharmaceutical ingredient and pharmaceutical dosage form. An effective separation was achieved on pre-coated silica gel HPTLC plates by using n-butanol:acetic acid:water (8:0.5:1.5 v/v/v). The spots were scanned densitometrically at 295 nm. The RF values of N-Acetyl cysteine and Taurine were found to be 0.29 and 0.52, respectively. Calibration curves were linear in the range of 30 - 180 and 100 - 600 ng/band for N-Acetyl cysteine and Taurine, correspondingly with correlation coefficients of 0.999. The developed method was validated as per ICH guidelines. The limits of detection were 11.24 and 63.40 ng/spot for NAC and TAU respectively. The method developed was found to be precise and specific for the simultaneous analysis of N-Acetyl cysteine and Taurine in pure and tablet dosage form.展开更多
Background: M. oleifera is a highly valued medicinal plant used widely from time immemorial to treat various ailments. However, with continued un-standardized use of the plant leaves, studies have reported organ toxic...Background: M. oleifera is a highly valued medicinal plant used widely from time immemorial to treat various ailments. However, with continued un-standardized use of the plant leaves, studies have reported organ toxicity to the liver, kidney and the heart. As communities continue to use M. oleifera leaves for its medicinal and nutritional values, there is need to find an antidote for its hepatotoxicity. Aim: The study established the reversal effect of N-Acetyl Cysteine (NAC) on M. oleifera aqueous leaf extract-induced hepatotoxicity in Wistar albino rats. Methods: Twenty-four (24) rats received a toxic dose (8.05 g/kg bwt) of M. oleifera leaf extract for 28 days to cause sub-acute hepatotoxicity. They were divided into 4 groups of 6 rats each. Group I received 1 ml normal (control group), Group II received 1000 ng/kg NAC, Group III received 1200 mg/kg NAC and Group IV received 1500 mg/kg NAC. Another group of 6 rats (Group V) received 0.75 mg/kg Paracetamol to cause hepatotoxicity. Group V (a positive control) received the prescribed clinical dose of 1200 mg/kg NAC which reverses the hepatotoxicity. All the NAC doses were given once a day intragastric for 7 days. On days: 1, 3 and 7 of receiving NAC, liver serum enzymes and bilirubin were measured. On day 7 the animals were sacrificed and liver tissue harvested for histopathology analysis. Results: A dose of 8.05 g/kg of M. oleifera leaf extract and 0.75 mg/kg Paracetamol were able to induce hepatotoxicity in Wister albino rats in 28 days. The M. oleifera extract induced hepatotoxic rats treated with NAC at doses of 1000 mg/kg, 1200 mg/kg and 1500 mg/kg, had a reduction in mean serum liver enzymes, plus reduced mean serum bilirubin levels. The liver histopathological analysis showed reduced inflammation after treatment with NAC for 3 and 7 days in the M. oleifera and paracetamol induced hepatotoxic rats. Conclusion: NAC can reverse M. oleifera leaf aqueous extract-induced sub-acute hepatotoxicity in Wistar Albino rats.展开更多
A series of novel N-[α-(isoflavone-7-O-)acetyl] amino acid methyl esters were prepared from the efficient and regioselective alkylation of isoflavones with chloroacetyl amino acid derivatives under mild condition.
文摘AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.
文摘AIMS To assess the protective effect of diallyl disulfide (DADS) and its combined use with N-acetyl-cysteine (NAC) on acetaminophen (APAP) hepatotoxicity in C57BL/6N (B6) mice pretreated with β naphthoflavone (BNF). METHODS B6 mice were divided into six groups and all compounds used were injected intraperitoneally. Except for control and APAP group (receiving APAP only), the other groups received an injection of APAP (350mg/kg) 48 hours after BNF (200mg/kg) and either of DADS (200mg/kg), or NAC (500mg/kg) or both DADS and NAC. DADS was given 2 hours before APAP and NAC was injected with APAP. The mean survival time was recorded and livers were examined histologically. Hepatic glutathione (GSH) levels and plasma ALT were also determined at different time points. To evaluate the effect of DADS or NAC on hepatic P450 induction by BNF, liver microsomes were prepared and 7 ethoxyresorufin O dealkylase (ERD) activity was determined using spectrofluorometrical methods. In vitro effect of DADS or NAC on ERD activity was assayed by directly incubating microsomal suspension with DADS or NAC of different concentrations. RESULTS APAP was not toxic to mice without BNF pretreatment, but caused severe liver necrosis and death of all BNF treated mice in 4 hours. A sharp depletion of GSH (approximately 62% of its initial content at 2 hours and 67% at 4 hours) and a linear elevation of ALT levels (536 8±29 5 Sigma units at 2 hours and 1302 5±74 9 at 4 hours) were observed. DADS and NAC given individually produced mild protection, resulting in prolonged survival, a slower decline of GSH level and a less steeper elevation of ALT level. All mice died eventually. Co administration of DADS and NAC completely protected mice. GSH level in this group lowered by about 35% and 30% at 2 and 4 hours, and ALT was 126±18 and 157 5±36 6 Sigma units at 2 and 4 hours. ERD activity in BNF treated mice was about 5 times that of the constitutive level determined in normal mice. Neither DADS nor NAC inhibited P450 1A1/1A2 induction as determined by their effect on the induction of ERD activity. In vitro assay indicates that DADS, but not NAC, was a potent inhibitor of ERD activity (IC 50 =4 6μM). CONCLUSIONS A combined use of both DADS and NAC produced full protection in BNF treated mice against APAP hepatotoxicity. The mechanism is that DADS inhibits P450 1A1/1A2 activity, but not induction, which substantially reduces production of NAPQI, while NAC enhances liver detoxifying capability via serving as a precursor of GSH and stimulating GSH synthesis.
文摘Specific, precise and sensitive TLC-Densitometric method was developed and validated for the simultaneous estimation of N-Acetyl cysteine and Taurine in active pharmaceutical ingredient and pharmaceutical dosage form. An effective separation was achieved on pre-coated silica gel HPTLC plates by using n-butanol:acetic acid:water (8:0.5:1.5 v/v/v). The spots were scanned densitometrically at 295 nm. The RF values of N-Acetyl cysteine and Taurine were found to be 0.29 and 0.52, respectively. Calibration curves were linear in the range of 30 - 180 and 100 - 600 ng/band for N-Acetyl cysteine and Taurine, correspondingly with correlation coefficients of 0.999. The developed method was validated as per ICH guidelines. The limits of detection were 11.24 and 63.40 ng/spot for NAC and TAU respectively. The method developed was found to be precise and specific for the simultaneous analysis of N-Acetyl cysteine and Taurine in pure and tablet dosage form.
文摘Background: M. oleifera is a highly valued medicinal plant used widely from time immemorial to treat various ailments. However, with continued un-standardized use of the plant leaves, studies have reported organ toxicity to the liver, kidney and the heart. As communities continue to use M. oleifera leaves for its medicinal and nutritional values, there is need to find an antidote for its hepatotoxicity. Aim: The study established the reversal effect of N-Acetyl Cysteine (NAC) on M. oleifera aqueous leaf extract-induced hepatotoxicity in Wistar albino rats. Methods: Twenty-four (24) rats received a toxic dose (8.05 g/kg bwt) of M. oleifera leaf extract for 28 days to cause sub-acute hepatotoxicity. They were divided into 4 groups of 6 rats each. Group I received 1 ml normal (control group), Group II received 1000 ng/kg NAC, Group III received 1200 mg/kg NAC and Group IV received 1500 mg/kg NAC. Another group of 6 rats (Group V) received 0.75 mg/kg Paracetamol to cause hepatotoxicity. Group V (a positive control) received the prescribed clinical dose of 1200 mg/kg NAC which reverses the hepatotoxicity. All the NAC doses were given once a day intragastric for 7 days. On days: 1, 3 and 7 of receiving NAC, liver serum enzymes and bilirubin were measured. On day 7 the animals were sacrificed and liver tissue harvested for histopathology analysis. Results: A dose of 8.05 g/kg of M. oleifera leaf extract and 0.75 mg/kg Paracetamol were able to induce hepatotoxicity in Wister albino rats in 28 days. The M. oleifera extract induced hepatotoxic rats treated with NAC at doses of 1000 mg/kg, 1200 mg/kg and 1500 mg/kg, had a reduction in mean serum liver enzymes, plus reduced mean serum bilirubin levels. The liver histopathological analysis showed reduced inflammation after treatment with NAC for 3 and 7 days in the M. oleifera and paracetamol induced hepatotoxic rats. Conclusion: NAC can reverse M. oleifera leaf aqueous extract-induced sub-acute hepatotoxicity in Wistar Albino rats.
文摘A series of novel N-[α-(isoflavone-7-O-)acetyl] amino acid methyl esters were prepared from the efficient and regioselective alkylation of isoflavones with chloroacetyl amino acid derivatives under mild condition.
