Cytotoxicity evaluation and hepatoprotective potential of bioassay guided fractions from Feronia limmonia Linn leaf

Objective

To evaluate the cytotoxicity and hepatoprotective potentials of extracts, fractions or isolated compound from the leaves of Feronia limonia (F. limonia).

Methods

Qualitative phytochemical analysis of extracts, fractions or compound was performed by means of thin layer chromatography and spectroscopic assays. The % purity of compound was measured by analytical HPLC. Extracts, fractions or compound have been individually evaluated for their cytotoxicity effects (10, 20, 100, 250, 500, 750 and 1 000 µg/mL). Based on the inhibitory concentration (IC₅₀) obtained from the cell viability assay, graded concentrations of extracts, fractions or isolated compound were assessed (10, 20, 50, 100, 200 µg/mL) for its hepatoprotective potential against CCl₄-induced hepatotoxicity by monitoring activity levels of serum glutamatic pyruvatic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT).

Results

Results indicated that the methanol extract of F. limonia was non-toxic and hepatoprotective in nature as compared with the petroleum ether extract. The acetone fraction of methanolic extract also showed similar properties but the subsequent two fractions were cytotoxic. However, the pure compound isolated from the penultimate fraction of methanolic extract was non-toxic and hepatoprotective in nature. Biochemical investigations (SGOT, SGPT) further corroborated these cytological observations.

Conclusions

It can be concluded from this study that F. limonia methanol extract, some fractions and pure isolated compound herein exhibit hepatoprotective activity. However, cytotoxicity recorded in the penultimate fraction and investigation of structural details of pure compound warrants further study.     

141例肝病患者的SGOT与SGPT比值测定观察

作者对141例肝病患者进行SGOT与SGPT检测并计算其比值,结果表明,急性肝炎、慢迁肝、慢活肝、肝硬化、肝癌的SGOT/SGPT值差异有高度显著性(p<0.01),认为对各种肝病的诊断和判断预后及对病毒性肝炎的临床分型等有重要参考价值。     

肝病冲剂对实验性肝损伤的保护作用

肝病冲剂能明显抑制四氯化碳(Ccl_4)所致动物血清谷丙转氨酶(SGPT),谷草转氨酶(SGOT),乳酸脱氢酶(LDH)的升高、减轻肝组织病理性损伤。对急性肝损伤具有保护作用。     

Toxicological methods

Toxicity protocols intended to cover several countries may be complex. The long-term study has changed relatively little in 20 years, but has been refined through, e.g., routine ophthalmoscopy. Closer chemical control throughout a study is advocated. Dosage form, route and frequency of administration all affect toxicity. “Effect level” and “maximum tolerated dose” remain valuable concepts. In certain instances, experimental animals may be more sensitive than man. Toxicological pathology is comparative rather than diagnostic, and extrapolation to man of tumorigenicity may be difficult. Tetratogenicity is exerted through a susceptible genetic locus.     

SULFONAMIDES IN BUFFALOES: EFFECT ON CERTAIN BLOOD CONSTITUENTS AND SERUM ENZYMES

1. Three groups of four clinically healthy buffaloes were injected with sulphadiazine, or sulphadimidine, or sulphathiazole in a single dose of 100 mg/kg body weight. 2. Changes in the serum enzyme activities (SGOT, SGPT and alkaline phosphatase) observed with the tested sulphonamides were insignificant, except for increases in SGOT level 6 h after sulphathiazole injection, and in GOT/GPT ratio 30 min and 24 h after sulphadimidine injection. 3. The creatinine level was not affected in sulphonamide-injected animals. All blood samples collected 15 min to 24 h after sulphathiazole injection showed marked increase in glucose and urea levels. Concerning the other two sulphonamides, no significant change was observed in these parameters except for an increased glucose level 24 h after sulphadiazine injection.     

Inhibition of methylprednisolone elimination in the presence of erythromycin therapy

Methylprednisolone elimination is reduced in the presence of treatment with troleandomycin (TAO), a macrolide antibiotic. To assess whether a similar interaction occurs with a more commonly used and less hepatotoxic macrolide antibiotic, erythromycin, we evaluated methylprednisolone pharmacokinetics before and after a 1 wk course of erythromycin base in nine adolescent patients with chronic asthma. These data were compared to results of studies of the troleandomycin methylprednisolone interaction evaluated in 10 adolescent asthmatic patients. Methylprednisolone clearance and apparent volume of distribution were significantly decreased and mean residence time and half-life significantly increased in the presence of both erythromycin and troleandomycin. The latter caused greater inhibition of methylprednisolone elimination. A nonlinear pattern of methylprednisolone disposition was observed in the presence of concomitant macrolide antibiotic administration. Addition of erythromycin base to methylprednisolone therapy results in inhibition of methylprednisolone elimination and may potentially increase the beneficial and adverse effects of this corticosteroid.     

乙肝康复冲剂的药理作用研究

乙肝康复冲剂由黄芪、白花蛇舌草等十味中药组成。研究证明,该药可明显增加大鼠胆汁分泌量,降低四氯化碳所致动物血清谷丙转氨酸(SGPT),谷草转氨酶(SGOT),乳酸脱氢酶(LDH)的升高、减轻四氯化碳对肝组织的损伤;促进肝脏对磺溴酞钠(BSP)的排泄,对急性肝损伤有明显保护作用。     

Protection against carbon tetrachloride-induced hepatotoxicity by pretreatment with methylmercury hydroxide

Pretreatment of rats with methylmercury hydroxide (MMH) (15 mg/kg s.c. for 2 days) protected against hepatotoxicity due to the inhalation of CCl4 vapor (4800–6100 ppm for 2 h). This was evidenced by lessening of the changes due to CCl₄ in liver glucose-6-phosphatase, serum glutamic oxal-acetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum isocitrate dehydrogenase and serum sorbitol dehydrogenase. Decreases in p-nitroanisole demethylation and cytochrome P-450 were also altered. Lipid peroxidation due to CCl₄ was decreased by MMH. These biochemical indices of protection were supported by histopathological observations.These results lend further support to the concept that metabolism of CCl₄ is necessary for its hepatoxicity.     

The toxicity of dimethyl sulphoxide (DMSO) for the dog,pig, rat and rabbit

Dimethyl sulphoxide (DMSO) was tested for oral toxicity in rats and dogs, and dermal toxicity in rabbits and pigs. Oral administration was by gastric intubation as a 50% aqueous solution, 5 days/week at levels equivalent to 9.0, 3.0 or 1.0 ml undiluted DMSO/kg/day. For dermal application 50% and 90% aqueous solutions were used to give levels equivalent to 8.1, 4.5, 2.7 or 1.5 ml DMSO/kg/day, as one daily application for rabbits, and divided into two applications/day for pigs. Dogs were dosed for approximately 2 years and pigs for 1 year, although half the animals of both species were dosed for only 18 weeks. Rats were dosed for 18 months, but some were used for interim sacrifice after a year. Rabbits received applications to normal and abraded skin for 6 months.Minor changes in bodyweight and haematological values were observed, together with a physiological diuretic response to DMSO, but the target organ was the eye, principally the lenticular nucleus. Ocular effects in dogs started after 5–10 weeks dosing at 9 ml/kg and consisted of central (nuclear) lens changes with alteration of the refractive index (myopia); transitory equatorial opacities during the 5th month; central (nuclear) opalescence; and changes in the vitreous humour. Similar changes occurred more slowly at 3 ml/kg, the alterations to the vitreous being first observed after 9–10 months at this level. Progressive nuclear refractive changes occurred after dosing for considerably longer than 6 months at 1 ml/kg, but none of the animals in this group manifested the opalescence. Biochemical investigation of the lenses revealed reduction of soluble protein (mainly α-crystallin), glutathione and water levels, and an increase of insoluble protein. Evidence of recovery was limited mainly to a reduction in the number of dioptres needed to correct nuclear refractive change. Cessation of dosing led to regression of refractive nuclear changes but did not prevent the appearance of opalescence at 3 ml/kg and above.Dogs were the most severely affected of the 4 species, with nuclear effects at 1 ml/kg, extensive changes in the lens, and involvement of the vitreous. Pigs and rabbits were affected by dose levels of 2.7 ml/kg and 1.5 ml/kg respectively. Rats occasionally showed minimal changes at 9 ml/kg.The importance of the findings in dogs is discussed in relation to general toxicology protocols. It is emphasised that reversibility of signs, and adequate duration of administration, must both be considered when ascertaining whether changes occur at levels approximating to those of human intake.     

人体血清鸟氨酸氨基甲酰转移酶正常值测定

本文报道126例献血员血清鸟氨酸氨基甲酰转移酶(SOCT)活性测定。用本法测定SOCT活性灵敏度与精确度高,重现性好,测得的SOCT正常值范围可靠、根据国外资料报道,SOCT作为肝脏病的酶学诊断指标,比SGPT和SGOT灵敏度高,特异性强。