Fotokemijska toksičnost lijekova namijenjenih okularnoj uporabi

The present investigation was undertaken to evaluate the possible ocular phototoxicity of drugs used in ophthalmic formulations. Sulphacetamide, ketoconazole, voriconazole, diclofenac, and ketorolac were assessed in the concentrations available in the market for their ocular use. The suitable models viz Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) test, Isolated Chicken Eye (ICE) test, and Red Blood Cell (RBC) haemolysis test as recommended by ECVAM, ICCVAM, and OECD guidelines were performed. Results of HET-CAM and ICE tests suggest that sulphacetamide is moderately toxic in the presence of light/UV-A and very slightly irritant without irradiation. Ketoconazole and voriconazole were found slightly irritant in presence of light/UV-A and non-irritant in dark. Diclofenac and ketorolac demonstrated slight irritancy in the light and were found to be non-irritant in dark. The results suggest that some of the drugs have potential toxic effect in the presence of light. The extent of phototoxicity might get extended when used for longer time. The recommendation is that these drugs should be stored and used in the dark for a specified time and be labelled with specific instructions for patients, especially for those working longer in the sunlight.Cilj ovog ispitivanja bio je istražiti moguću okularnu fototoksičnost lijekova koji se koriste u oftalmološkim formulacijama. Sulfacetamid, ketokonazol, vorikonazol, diklofenak i ketorolak ispitivani su u koncentracijama koje su dostupne na tržištu u njihovom obliku koji je namijenjen za okularnu uporabu. Primijenjeni su testovi iritacije na kokošjem jajetu (Hen’s Egg Test Chorioallantoic Membrane - HETCAM), izoliranom kokošjem oku (Isolated Chicken Eye - ICE) i test hemolize crvenih krvnih stanica (Red Blood Cell - RBC) prema preporukama ECVAM-a, ICCVAM-a i OECD-a. Rezultati HET-CAM i ICE testova upućuju na umjerenu toksičnost sulfacetamida u prisutnosti svjetla/UV-A te vrlo blagu iritaciju u mraku. Ketokonazol i vorikonazol pokazali su blagu iritaciju u prisutnosti svjetla/UV-A te nikakvu iritaciju u mraku. Diklofenak i ketorolak pokazali su blagu iritaciju na svjetlu i nikakvu iritaciju u mraku. Rezultati upućuju na moguću toksičnost nekih od navedenih lijekova u prisutnosti svjetla. Razmjer fototoksičnosti može biti povećan pri produljenoj uporabi lijeka. Preporučuje se čuvati navedene lijekove na zatamnjenome mjestu te ih označiti odgovarajućim uputama za korištenje, osobito za osobe koje su dulje vrijeme izložene sunčevoj svjetlosti

Transcutaneous Vagus Nerve Stimulation Regulates the Cholinergic Anti-inflammatory Pathway to Counteract 1, 2-Dimethylhydrazine Induced Colon Carcinogenesis in Albino wistar Rats

The present work was undertaken to study the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on 1, 2-dimethyhydrazine (DMH) induced colon cancer and role of the cholinergic anti-inflammatory pathways (CAP) in the same. Groups of rats were randomly divided into ten groups (n = 8). DMH administration was very well apparent for autonomic dysfunction as observed through distorted hemodynamic (electrocardiogram and heart rate variability), increased aberrant crypt foci and flat neoplastic lesions (methylene blue staining, scanning electron microscopy and Hematoxylin and eosin staining). DMH administration was also recorded for per-oxidative damage. taVNS application restored the autonomic function, cellular morphology and curtailed the oxidative damage. DMH application conspicuously inhibited the mitochondrial apoptosis which was restored back after taVNS application, when scrutinized through immunoblotting and quantitative real time polymerase chain reaction studies. taVNS application up-regulated the CAP as perceived through increased expression for α7 nicotinic acetylcholine receptor(α7nAchR) and decreased expression for nuclear factor kappa-ligand-chain-enhancer of activated B cells (NFκBp65), tissue necrosis factor-α and high mobility group box-1 at protein and mRNA levels. All in all, taVNS up-surged the CAP to counteract DMH induced colon carcinogenesis. Among all the stimulation parameters used, taVNS 3 (pulse width-1 ms, frequency-6 Hz, voltage-6 v, duration-240 min) was observed to be the most effective. Since only chemotherapy and surgery are available options for management of CRC, which are troublesome and painful, there is currently no non-invasive method available for management of CRC. Results of the current study affirmed the effectiveness of taVNS against DMH induced colon cancer. The present study established taVNS as a novel and non-invasive approach toward the management of CRC

Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME

Effect of <i style="">Aloe vera</i> (<i style="">Aloe barbadensis</i> Miller) gel on doxorubicin-induced myocardial oxidative stress and calcium overload in albino rats

260-268Administration of a single dose of doxorubicin (DOX) (7.5 mg/kg, iv) produces cardiotoxicity, manifested biochemically by significant decrease in blood glutathione (GSH) and tissue GSH along with elevated levels of serum lactate dehydrogenase (LDH) and serum creatine phosphokinase (CPK). In addition, cardiotoxicity was further confirmed by significant increase in lipid peroxides expressed as malondialdehyde (MDA, secondary indicator of lipid peroxidation), tissue catalase and tissue superoxide dismutase (SOD). Administration of A. vera gel (100 and 200 mg/kg) orally for 10 days produced a significant protection against cardiotoxicity induced by DOX evidenced by significant reductions in serum LDH, serum CPK, cardiac lipid peroxides, tissue catalase and tissue SOD along with increased levels of blood and tissue GSH. The results revealed that A. vera gel produced a dose dependent protection against DOX induced cardiotoxiaty

Kaithwas G. Effect of Perilla frutescens Fixed Oil on Experimental Esophagitis

The present study was undertaken to elucidate the effect of Perilla frutescens fixed oil on experimental esophagitis in albino rats. A group of rats ( = 6), treated with control vehicle (0.9% NaCl in double distilled water, 3 mL/kg, i.p.) and Perilla frutescens fixed oil (100%) (1, 2, and 3 mL/kg, i.p.), or pantoprazole (30 mg/kg, i.p.), were subjected to pylorus and forestomach ligation. Animals were sacrificed after 6 h and evaluated for the gastric pH, volume of gastric juices, total acidity, esophagitis index and free acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH, catalase, and SOD. Treatment with fixed oil significantly inhibited the gastric secretion, total acidity, and esophagitis index. The oil also helped to restore the altered levels of oxidative stress parameters to normal. The present study also makes evident the in vitro antihistaminic and anticholinergic activity of alpha linolenic acid (ALA) (18 : 3, − 3) on isolated rat ileum preparation. The lipoxygenase inhibitory, histamine antagonistic, antisecretory (anticholinergic), and antioxidant activity of the oil was attributed for its efficacy in reflux esophagitis

Effect of Perilla frutescens Fixed Oil on Experimental Esophagitis in Albino Wistar Rats

The present study was undertaken to elucidate the effect of Perilla frutescens fixed oil on experimental esophagitis in albino rats. A group of rats (n=6), treated with control vehicle (0.9% NaCl in double distilled water, 3 mL/kg, i.p.) and Perilla frutescens fixed oil (100%) (1, 2, and 3 mL/kg, i.p.), or pantoprazole (30 mg/kg, i.p.), were subjected to pylorus and forestomach ligation. Animals were sacrificed after 6 h and evaluated for the gastric pH, volume of gastric juices, total acidity, esophagitis index and free acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH, catalase, and SOD. Treatment with fixed oil significantly inhibited the gastric secretion, total acidity, and esophagitis index. The oil also helped to restore the altered levels of oxidative stress parameters to normal. The present study also makes evident the in vitro antihistaminic and anticholinergic activity of alpha linolenic acid (ALA) (18 : 3, n−3) on isolated rat ileum preparation. The lipoxygenase inhibitory, histamine antagonistic, antisecretory (anticholinergic), and antioxidant activity of the oil was attributed for its efficacy in reflux esophagitis