Systematic Reviews of Animal Models: Methodology versus Epistemology

Greek, Ray; Menache, André

doi:10.7150/ijms.5529

Cited by 181 publications

(134 citation statements)

References 179 publications

(132 reference statements)

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“…Preclinical data exhibit potent antiinflammatory, antifibrotic, antiviral, and antioxidative properties of silymarin [19]. However, the predictive value of animal and in vitro models is sometimes misleading and may have led to failures of translation into the clinical practice for many years [20]. A classic example was the aforementioned role of silymarin in chronic viral hepatitis [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Not all of the published studies fulfill high scientific standards. Once we cite studies with less clear-cut scientific evidence in this review, we describe the limitations and focus on the bits of evidence which may fit or not into a logical puzzle of the current scientific knowledge with respect to silymarin [20]. Furthermore, to be of clinical interest, experimental data on silymarin should be obtained at doses and administration routes comparable to those used in clinical settings.…”

Section: Introductionmentioning

confidence: 99%

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The potential of silymarin for the treatment of hepatic disorders

et al. 2016

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Silymarin has long been used as a hepatoprotective remedy. Chronic toxicity studies in rodents have confirmed that silymarin has a very low toxicity. These data support its history as a safe medication in hepatic diseases. In the last years, several studies expanded our understanding of the pharmacology of silymarin and its molecular mechanisms of action. These new insights may affect the handling of silymarin in clinical studies and daily practice. Additionally, scientific knowledge in hepatology is constantly evolving with, particularly, an increase in the field of non-alcoholic fatty liver disease which is considered today as the most frequent liver disease worldwide. In this review, we will describe scientific evidence for the effectiveness of silymarin in hepatic disorders. We will focus on silymarin's pharmacological effects in non-alcoholic fatty liver disease and on its well described effects in alcoholic liver disease and acute intoxications, e.g. with Amanita species. We will discuss the relevance of pharmacological data as a function of doses or concentrations required for a given effect and of concentrations achieved in the target tissues. Many pharmacological effects of silymarin can be attributed to effects downstream or upstream of its antioxidative and membrane-stabilizing properties. However, despite promising new experimental and clinical data further clinical studies are required including long-term observations and the application of hard clinical endpoints such as survival rates, to further support silymarin's use for the treatment of hepatic diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The potential of silymarin for the treatment of hepatic disorders

et al. 2016

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“…Concerns have been raised worldwide for the use of different animals such as Chimpanzee citing their lack of predictability and also claims of irrelevance for human behaviors are majorly under debate [24]. Criticisms have been raised in the use of animal models has been summarized with the following errors of conception [25] Failures in animal models usually are because of disparities in disease specificity between the animal models and clinical trials that lead to inadequate data and incorrect conclusions on the outcomes. Thus there are critical parameters required to be monitored such as Sample size calculation, Monitoring of physiological parameters, eligibility criteria etc.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Research: A Rise or Dawn

Manjunath¹

2018

PPIJ

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IntroductionComplex processes are involved in developing a new drug along with its time and costs consumption. Prior to launching, it requires variety of evidences to show its potential activity [1]. Key step in drug discovery is considered to be the target discovery which ranges from molecular entities to biological phenomenon [2]. As there are urges in translating scientific discoveries into practical importance, preclinical studies using animal models play an important role in evaluating the efficacy and safety under clinical scenario [3]. After enormous debates, it is concluded that the benefits of animal research is worth to manage public health and medical research [4]. Subsequently, animal studies are justifiable if done in a way to minimize pain in animal models and wherever applicable alternative methods are explored and avoiding unnecessary cruel treatment to animals [5]. However, various reports have enforced on the failures of trails that has never capitalized after thorough observation of safety and efficacy in animal models which mainly portraits the requirement of robustness in preclinical studies [6][7][8][9][10]. For instance, reports say that, almost 95% of drugs that enter clinical trials related to stroke or septic shock do not get launched in the market though enormous expenditures have been dealt with the basic studies and drug discoveries [11] and similarly, the average success rate in clinical cancer trials is less than 8% after preclinical estimation [10].Still it is recommended to circumvent preclinical studies because of the scientific, practical and ethical reasons, to conduct studies in humans [6], and thus prior to this attempt, preclinical drug combination studies in vitro and/or in animals has to be carried out to obtain the base for studies in human [12]. Though the debate over use of the animals in medical experiments has a long and unpleasant history, eminent researches along with Nobel Prize winners have signed a declaration provided by the Research Defense Society has made claim that experiments on animals have made important contribution to advances in medicine and surgery [13]. Research focused on pain research has shown enormous rate of failures and increased costs of drug development this is because of phenotypic differences and complexity in behavioral alterations along with the changes in daily activities and psychological disturbances [14,15]. Moreover, the test and models of nociception has been questioned in the aspect of appropriateness between tests, models and procedures [16]. Thus in order to develop robustness in pain management and to effectively gather required evidences, it is better to evaluate pain states in higher order preclinical species where we can predict whether biological mechanisms and specific compounds have relevance for clinical pain better than rodent species. The pain models in non-rodent species may enhance the speed, and in addition reduce costs along with the increased probable results for a successful analgesic development [17]. Hiccups in...

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“…EU ban on animal testing of cosmetic ingredients), such a transition is motivated by scientific considerations. Animals are often poor models for humans due to sometimes well-known qualitative and also quantitative differences in their physiology and metabolism (Coecke et al, 2005;Pelkonen et al, 2009;Greek and Menache, 2013;Coecke et al, 2014). In order to use human in vitro toxicity data for human risk assessment, a stronger focus on internal exposure (e.g.…”

Section: -Introductionmentioning

confidence: 99%