Olanzapine induced biochemical and histopathological changes after its chronic administration in rats

AbstractObjective: Olanzapine is a second generation antipsychotic acting mainly as a dopamine D2 and serotonine 5-HT2 receptors antagonist prescribed in the treatment of schizophrenia and various other psychiatric illnesses. Even though olanzapine is widely used in psychiatry, its effects on the architecture of pancreas, liver and kidneys are little known. The histology of pancreas especially has never been studied. For these reasons, the current study was designed to elucidate the toxic effects of chronic administration of olanzapine on pancreas, liver and kidneys and the enzymes released by these tissues in an escalating dose manner. Methods: Fourteen male rats were divided into two groups equally, the olanzapine group and the controls. Olanzapine was administered in a dose of 5mg/kg/d for the first eight weeks, 10mg/kg/d for next four weeks and 15mg/kg/d through the last two week period of 14weeks experiment. The controls received acidified saline only. Both the groups received restricted diet (20g/12h). The body weight and level of random blood sugar (RBS) were measured on a weekly basis. The levels of lipase, amylase, alanine transaminase (ALT) and aspartate transaminase (AST) were determined terminally. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Results: Significant loss in body weight, change in the level of random blood sugar (∗∗P<0.05, ∗∗∗P<0.001) and significant rise in amylase and lipase levels (∗P<0.05, ∗∗∗P<0.001) were observed. However, the same treatment has shown no significant change in the levels of alanine and aspartate transaminases (P>0.05). The pancreas has shown derangement of beta cells and fibrotic growth. A mild to moderate focal increase in glomerular cellularity, cellular proliferation and glomerular capsules with negligible basement membranes were observed in the kidneys. No changes were observed in the architecture of the liver. Conclusion: The findings of this study indicated that the incidence of adverse effects associated with olanzapine could be prevented/alleviated/delayed by allowing restricted diet

Novel hydroquinone derivatives alleviate algesia, inflammation and pyrexia in the absence of gastric ulcerogenicity

Purpose: To synthesize and characterize novel hydroquinone compounds that exhibit an aspirin-like pharmacological profile devoid of ulcerogenic side effects.Methods: Two novel hydroquinone derivatives, viz, 2,5-bis(piperidinomethyl)hydroquinone and 2,5- bis(pyrrolidinomet hyl)hydroquinone, were synthesized by refluxing hydroquinone, paraformaldehyde and secondary amines (piperidine or pyrrolidine) in ethanol. The structures were authenticated by infrared (IR) spectroscopy, elemental analysis, mass spectrometry (MS) and 1H and 13C nuclear magnetic resonance (NMR) spectroscopic techniques. The synthesized derivatives were evaluated for antinociceptive, anti-inflammatory and antipyretic activities along with gastric-ulcerogenicity using wellknown testing paradigms. Aspirin served as reference standard.Results: The newly synthesized hydroquinone derivatives, significantly attenuated tonic visceral chemically-induced nociception at 10 mg/kg (p &lt; 0.01, p &lt; 0.001), 20 and 40 mg/kg (p &lt; 0.001), inhibited the temporal-inflammatory reaction at 50 mg/kg (2 - 5 h, p &lt; 0.05, p &lt; 0.001), 100 and 150 mg/kg (1 - 5 h, p &lt; 0.05, p &lt; 0.01, p &lt; 0.001) in addition to alleviating the febrile-response at test doses during 0.5 h (p &lt; 0.05, p &lt; 0.01, p &lt; 0.001), 1 and 1.5 h (p &lt; 0.001) of the study period. The synthesized compounds exhibited improved gastric tolerability profile since they were devoid of aspirin-associated biochemical and ulcerative changes. The in silico studies predicted high binding affinity of the hydroquinone derivatives to the active site of the cyclooxygenase 2 (COX-2) enzyme.Conclusion: The synthesized hydroquinone compounds possess analgesic, antipyretic and antiinflammatory properties with low gastric-ulcerogenic potential. This may be credited to preferential inhibition of the COX-2 enzyme and the beneficial basic rather than acidic chemical nature of the compounds. However, further molecular studies are required to substantiate these findings.Keywords: 2,5-Bis(piperidinomethyl)hydroquinone], 2,5- is(pyrrolidinomethyl)hydroquinone, Antiinflammatory, Antinociceptive, Antipyretic, Gastric-ulcerogenicity, Algesi

Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms

Background: Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocininduced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms. Methods: PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia. Results: GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency. Conclusions: These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain. The antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and GABAergic mechanisms though a potential oleamide-sourced cannabimimetic involvement is also discussed

The Impact of CEO Duality and Financial Performance on CSR Disclosure: Empirical Evidence from State-Owned Enterprises in China.

This paper studies the effects of a firm’s financial performance (FP) and chief executive officer’s (CEO) duality on the quality of corporate social responsibility (CSR) disclosure in the context of state-owned enterprises (SOEs) among Chinese A-share-registered companies. The results depict a negative relationship between CEO duality and CSR disclosure. Our results demonstrate that better-performing firms disclose CSR information more frequently and of higher quality compared with firms with poor financial performance. This role of financial performance in the quality of CSR disclosure is generally valuable in public enterprises; however, it is relatively sluggish in state-owned enterprises the outcomes indicate that the dual leadership structure reduces assessments and renders CEOs less liable to their stakeholders. Therefore, this study offers valuable information and details for regulators to improve corporate governance and CSR from the perspective of stakeholder theory

Green R & D investment, ESG reporting, and corporate green innovation performance.

Given the contradictory empirical evidence on the relationship between green R&D expenditure and corporate Green Innovation performance (GIP), The present research study is a distinctive investigation into the moderating impacts of ESG reporting on this relationship. We utilized a data collection of 3,846, firm-year observations of A-share listed firms in China from 2016 to 2022 from CSMAR and Bloomberg databases. The firm's Corporate GIP is assessed and measured by looking at the total quantity of green patents. Lastly, models with multiple regression analyses and fixed effects were employed. The findings show that ESG reporting has a positive and significant impact on the association between corporate GIP and green R&D expenditure, implying its compensating and supportive function in the form of green signals in green outputs. This research could help executives and lawmakers, especially in developing countries to build innovative environmental strategies for business sustainability

CSR Disclosure: Effects of Political Ties, Executive Turnover and Shareholder Equity. Evidence from China

The context of China fosters different contextual factors, which influences the quality of corporate social responsibility (CSR) disclosure in comparison to firms across the rest of the world. Political ties at a corporate level are one of these vital factors. This paper studies the influence of firm-level political ties (PT) and executive turnover (ET) on the quality of CSR disclosure in the context of shareholding status of departing executive in Chinese listed A-share firms. Stakeholder and Agency theories are applied to the dissemination of CSR disclosures in Chinese firms whereby we used 20,578 firm-years interpretations of Chinese registered companies between 2012 and 2019. The results foster a negative link between executive turnover and quality of CSR disclosures. In addition, a negative relationship has been found between political ties and the quality of CSR disclosure. The findings disclose that the shareholding status of departing executive moderate the relationship between the impact of political ties and executive turnover on firms quality of CSR disclosure, whilst the effect of executive turnover on the quality of CSR disclosure was found more pronounced for firms whose departing executive held larger shareholding (SH). This study contributed to the literature on the quality of CSR disclosure while recognizing the negative effect of executive turnover on a firm’s quality of CSR disclosure for politically tied firms with a reinforcing moderating role of the shareholding status of departing executive

R&amp;D investment, corporate social responsibility disclosure and firm's green innovation performance:evidence from China

Given the contesting empirical literature on the relationship between Research and Development (R&amp;D) investment and firms' green innovation performance (GIP), the current research is a unique study to look at the moderating effects of corporate social responsibility disclosure (CSRD) on this relationship. We used dataset of 3248 firm-year observations of A-share listed firms in China from (2012-2020). The CSRD issued by Chinese Stock Exchange and the Accounting Research Database (CSMAR) is used to measure CSR information. The Corporate GIP of a firm is considered and measured by examining the total number of green patents. Finally, multiple regression and fixed effects models were used. The results reveal that CSRD has anaffirmative and significant impact on the relationship between corporate GIP and R&amp;D investment which implies the compensatory and supportive role of CSR strategies in shape of green signals in the green outcomes. This research could support managers and policymakers of underdeveloped nations inestablishing environmental innovation strategies for corporate sustainability.</p

Board Gender Diversity and Corporate Social Performance in Different Industry Groups: Evidence from China

This paper examines the heterogeneous links between board gender diversity and corporate social performance in different industries across China. OLS regression models are approximated using the data of Chinese industries from 2009 to 2015. Robustness test and two-stage least square (2SLS) methods are incorporated to cater for robustness and endogeneity. Board gender diversity (BGD) stimulates corporate social performance (CSP) of firms with environmental and social risk exposure regardless of critical mass and directors’ independence. It does so for firms with governance risk exposure while incorporating the critical mass effect and the director’s independence. Overall, the positive effect of BGD is prevalent in different industries at an aggregate level while considering firms with an overall ESG risk exposure. The findings imply that BGD can mitigate the ESG risk exposure in terms of enhancing the CSP and the advantage can be transpired with the inclusion of even one female director (independent or executive) to the board. The study also highlights that BGD enhances CSP in industries with more environmental and social risk exposure while doing so in industries with governance risk exposure after complementation by critical mass and independent director effects

How executive turnover influences the quality of corporate social responsibility disclosure?:Moderating role of political embeddedness: evidence from China

This study investigated the relationship between executive turnover (ET) and quality of corporate social responsibility disclosure (CSRD) at the firm level. The role of political embeddedness (PE) in the association between ET and CSRD quality in Chinese listed A-share firms is also inspected. We employed 20,850 firm’s/year observations between 2010 and 2016. An inverse relationship was found between ET and CSRD quality as well as PE and CSRD quality. In addition, the study findings disclose that corporate PE moderates the relationship between ET and a firm’s CSRD quality whilst the impact of ET on a company's CSRD quality was found more pronounced for firms with a low level of corporate PE. This examination adds to the literature on CSRD quality under the premise of normative stakeholder theory and leads to the conclusion that the political link of departing executives is an active participant in the exacerbation of CSRD quality in PE firms of China. This implies a reinvigoration of the roles of decision-makers for sustainable CSR assurance

Additional file 1: of Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms

Passiflora incarnata plant, grown in the botanical garden of the Department of Pharmacy, University of Peshawar, Pakistan. (DOCX 637 kb