Trease and Evans' pharmacognosy

Isoniazid (INH) is an antituberculosis drug associated with idiosyncratic liver injury in susceptible patients. INH-induced hepatotoxicity remains a significant clinical problem, but the underlying mechanisms are still unclear, despite the growing evidence that INH and/or its major metabolite, hydrazine, play an important role in hepatotoxicity.

Hepatotoxicity mechanisms of isoniazid: A mini-review.

Liver is the largest and important organ in the body, involved in the metabolism of food and drugs. Liver diseases are potentially life threatening for humans. The etiology of liver disorder varied due to different reasons like autoimmune disorder, viral infection, toxic chemical, and due to changing diet style. Liver injury produces pathological changes like increase level of SGOT, SGPT, TB and generation of free radical radicals. A better understanding of primary mechanisms is mandatory for designing of new therapeutic drugs. Therefore, animal models are being developed to mimic human liver diseases. Animal models are being used for several decades to study the pathogenesis of liver disorders and related toxicities. In this review, we revealed various animal models with their merits and demerits. Our main focus is to explore all new and traditional animal models under broad classification like non-invasive, invasive and genetic models which directly or indirectly produce hepatotoxicity.

Animal models of hepatotoxicity

Liver diseases have become a major global health challenge and may be triggered by several toxic chemicals, which include chemotherapeutic agents, thioacetamide, carbon tetrachloride, certain antibiotics, excessive alcohol consumption, and pathogenic microbes. Hence, safeguarding a healthy liver is vital for good health and well-being. Despite advances in pharmacology, the demerits associated with synthetic drugs have outshone the merits. Treatment of liver diseases based on modern medical principles is becoming ineffective and also associated with adverse effects of long-term use, in addition to prohibitive costs in developing countries. Thus, exploring medicinal plants which are easily available and cheap and do not involve strenuous pharmaceutical production processes appears to have gained worldwide attention as alternative therapeutic agents for the diseases. Consequently, emphasis has been placed on folkloric herbs with high efficacy, low toxicity, and cost-effectiveness. In this paper, literature search was conducted using various databases such as Google Scholar, ISI Web of Knowledge, and PubMed; we carried out a comprehensive review on existing information on some medicinal plants around the world with hepatoprotective prospects. Phytochemical compounds with hepatoprotective effects were also discussed, and finally, the future work in the field was also highlighted.

A Review on Some Medicinal Plants with Hepatoprotective Effects

Isoniazid (INH) remains the core drug in tuberculosis management, but serious hepatotoxicity and potentially fatal liver injury continue to accompany INH consumption. Among numerous theories that have been established to explain INH-induced liver injury, an inflammatory stress theory has recently been widely used to explain the idiosyncrasy. Inflammatory stress usually sensitizes tissues to a drug's toxic consequences. Therefore, the present study was conducted to verify whether bacterial lipopolysaccharide (LPS)-induced inflammation may have a role in enhancing INH hepatotoxicity. While single INH or LPS administration showed no major toxicity signs, INH-LPS cotreatment intensified liver toxicity. Both blood biomarkers and histological evaluations clearly showed positive signs of severe liver damage accompanied by massive necrosis, inflammatory infiltration, and hepatic steatosis. Furthermore, elevated serum levels of bile acid associated with the repression of bile acid synthesis and transport regulatory parameters were observed. Moreover, the principal impact of cytochrome P450 2E1 (CYP2E1) on INH toxicity could be anticipated, as its protein expression showed enormous increases in INH-LPS-cotreated animals. Furthermore, the crucial role of CYP2E1 in the production of reactive oxygen species (ROS) was clearly obvious in the repression of hepatic antioxidant parameters. In summary, these results confirmed that this LPS-induced inflammation model might prove valuable in revealing the hepatotoxic mechanisms of INH and the crucial role played by CYP2E1 in the initiation and propagation of INH-induced liver damage, information which could be very useful to clinicians in understanding the pathogenesis of drug-induced liver injury.

Role of Inflammatory and Oxidative Stress, Cytochrome P450 2E1, and Bile Acid Disturbance in Rat Liver Injury Induced by Isoniazid and Lipopolysaccharide Cotreatment.

Hepatoprotective potential of ethanolic extract of Ziziphus oenoplia (L.) Mill roots against antitubercular drugs induced hepatotoxicity in experimental models

Soybean has emerged as a potential crop for changing the economical position of the farmers in India particularly in Madhya Pradesh. Although ecological condition of the state are congenial for soybean production but the yield is substantially low, despite of best management practices. The poor weed management practices deprive the crop of its major requirement of nutrients, soil moisture, sunlight and space which results poor crop growth and yield. Being a rainy season crop, it has high yielding capacity but weed infestation is one of the major constraints in soybean cultivation (Bhan et al. 1974). The weed, if not controlled during critical period of weed crop competition, there may be reduction in the yield of soybean from 58-85% depending upon type and weed intensity (Singh and Singh 1987, Kolhe et al. 1998). Looking to the present need of post-emergence herbicides for higher soybean yield, this study was undertaken.

Efficacy of early post-emergence herbicides against associated weeds in soybean

Rice (Oryza sativa L.) being a major food crop of Madhya Pradesh is cultivated on 1.68 million ha with production of 1.56 million tones (Anonymous 2009). Direct seeding of rice has more benefits as compared to traditional transplanting. However, weeds are one of the limiting factors in directseeded rice, which reduce the yield up to 50-100%. Bispyribac-sodium is known to be effective against many annual and perennial grasses, sedges, and broad-leaved weeds in rice (Yadav et al. 2009). However, meager information is available for Kymore plateau and Satpura Hills Zone of M.P., hence the present investigation was undertaken. METHODOLOGY A field experiment was carried out during Kharif season of 2010 at Jawaharlal Nehru Kirshi Vishwa Vidyalaya, Jabalpur (M.P.) to test the efficacy of bispyribac-sodium against weeds. Ten treatments consisting of bispyribac-Na at varying doses along with conventinonal herbicides (butachlor) and hand weeding were arranged in a randomised block design with three replications. Rice variety ‘IR 64’ was direct-seeded these treatments, which was significantly lower than all other treatments. These results are in conformity with the findings of Yadav et al. (2009). Maximum weed index (66.4%) was recorded in unweeded check. Among the herbicidal treatments, bispyribac-sodium 80 g/ha recorded minimum weed index (5.2%). This clearly indicated that weeds were controlled effectively under bispyribac-sodium 80 g/ha.

Efficacy of bispyribac-sodium on weed flora and yield of drilled rice

In soybean, weeds are controled by cultural, mechanical and chemical methods either alone or in combination of more than one methods. Weed management through manual weeding or hoeing although effective in reducing weed competition but it is not free from several limitations such as non-availability of sufficient manpower during peak periods, high labour cost, time consuming and not feasible under heavy soils and high rainfall areas. Moreover, mechanical weeding disturbs the physical conditions of the soil and cause mechanical injury to roots and shoots. To overcome these problems, weed control in soybean by chemicals is preferred, which is effective, cheaper and many times faster than the conventional methods. A field experiment was conducted during rainy season of 2009-10 at Research Farm, Jawaharlal Nehru Krishi Vishwa Vidyalaya, Jabalpur (Madhya Pradesh). The soil of the experimental field was sandy clay loam in texture, neutral in reaction having 0.68 per cent organic carbon. The soil was low in available N (215 kg/ha), P (9.20 kg/ ha) and medium in K (318.0 kg/ha). Nine treatments, viz. imazethapyr (75 g/ha), imazethapyr (100 g/ha) imazethapyr + adjuvant (75 g + 1 l/ha) imazethapyr + adjuvant + ammonium sulphate (100 g + 750 ml + 1 kg/ha), chlorimuronethyl (9.7 g/ha), fenoxoprop-ethyl (67.5 g/ha), weed free (HW at 30 DAS) and weedy check were tested in randomized block design with three replications. Healthy seeds (70 kg/ha) of soybean cv. ‘JS 97.52’ were treated before sowing with thiram at the rate of 3 g/kg and sown in furrows opened manually at 30 cm apart rows. The soybean crop fertilized with 20 kg N (urea) : 60 kg P2O5 (single super phosphate) and 20 kg K2O (muriate of potash) at the time of sowing. The total rainfall received during the period of experimentation was 1339.3 mm. The quadrate of 0.25 m2 was used to count the weeds in each plot. The data were transformed and expressed in per square meter. The percentage of weed flora was estimated from weedy check. Weed control efficiency (WCE) was estimated by the formula given by Mani et al. (1973). The weed flora of the experimental field consisted of both grassy weeds, viz. Cyperus rotundus, Digitaria sanguinallis and Eleusine Indica and broad-leaved weeds, viz. Portulaca oleracea and Eclipta alba.

Bioefficacy of post-emergence herbicides in soybean

The Front line Demonstration undertaking the basic principle of extension education “Learning by doing and seeing is believing” are back bone of the transfer to technology. The present study was undertaken in Kymore plateau and satpura hills of Madhya Pradesh under Krishi vigyan Kendra Chhindwara, Betul and Panna districts. Eight villages were selected from identified districts. The study was carried out to know the yield gaps between improved package and practices (IP) and framers practice (FP) of soybean crop. The yield of soybean in IP under different conditions ranges from 15.85 to 20.58 q/ha, whereas, in FP ranges from 11.2 to 16.55 q/ha. The 22 to 67.85 percent increase in yield with IP over FP was recorded. The extension gap ranging between 3.7 – 7.6 q/ha during the period of study. The trend to technology gap reflected the farmer’s cooperation in carrying out such demonstrations with encouraging results in subsequent years. The cost benefit ratio was 1.31 to 3.69 under demonstration, while it was 0.78 to 2.80 under control plots.

https://www.thepharmajournal.com/archives/2018/vol7issue10/PartB/7-9-37-404.pdf

Impact of production technology on productivity and profitability of soybean under Kymore Plateau and Satpura hills Agro Climatic zone of Madhya Pradesh

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