Folic acid inhibits necrosis and apoptosis in ischemic and reperfusion induced injury in rat liver

Chattopadhyay, Pronobesh,Shukla, Gunjan,Wahi, Arun Kumar Kyung Hee Oriental Medicine Research Center 2009 Oriental pharmacy and experimental medicine Vol.9 No.1

Temporary clamping of the portal triad is a common strategy to minimize bleeding during liver transplantation. Increasing evidences suggests that oxygen derived free radicals and reintroduction of oxygen in ischemic tissue lead to ischemic and reperfusion injury (I/R) and lead to apoptosis and necrosis. Adult Wistar rat subjected to 60 min of partial liver ischemia followed by three hour reperfusion. Eighteen Wister rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion group (II) (n = 6), folic acid treated group (1 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n = 6). Apoptotic and necrotic hepatocytes, mitochondrial antioxidant enzymes were measured. Liver injury was assessed by alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology and electron microscopy. An ischemic and reperfusion hepatocellular injury was indicated by increased serum-ALT, AST, histopathology and electron microscopy studies. Apoptotic and necrotic cells were increased which was revealed by flow cytometry in I/R group. Pre- treatment with folic acid significantly decreased serum -ALT, AST levels, apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Histopathology and TEM studies showed markedly diminished hepatocellular injury in folic acid pretreated rats during the hepatic I/R, which reached a level comparable to saline-treated rat of sham operated group. On the basis of our findings it may be concluded that folic acid afforded significant protection from necrosis and apoptosis in I/R injury.

Folic acid inhibits necrosis and apoptosis in ischemic and reperfusion induced injury in rat liver

Pronobesh Chattopadhyay,Gunjan Shukla,Arun Kumar Wahi 경희대학교 융합한의과학연구소 2009 Oriental Pharmacy and Experimental Medicine Vol.9 No.1

Temporary clamping of the portal triad is a common strategy to minimize bleeding during liver transplantation. Increasing evidences suggests that oxygen derived free radicals and reintroduction of oxygen in ischemic tissue lead to ischemic and reperfusion injury (I/R) and lead to apoptosis and necrosis. Adult Wistar rat subjected to 60 min of partial liver ischemia followed by three hour reperfusion. Eighteen Wister rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion group (II) (n = 6), folic acid treated group (1 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n = 6). Apoptotic and necrotic hepatocytes, mitochondrial antioxidant enzymes were measured. Liver injury was assessed by alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology and electron microscopy. An ischemic and reperfusion hepatocellular injury was indicated by increased serum-ALT, AST, histopathology and electron microscopy studies. Apoptotic and necrotic cells were increased which was revealed by flow cytometry in I/R group. Pre- treatment with folic acid significantly decreased serum -ALT, AST levels, apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Histopathology and TEM studies showed markedly diminished hepatocellular injury in folic acid pretreated rats during the hepatic I/R, which reached a level comparable to saline-treated rat of sham operated group. On the basis of our findings it may be concluded that folic acid afforded significant protection from necrosis and apoptosis in I/R injury. Temporary clamping of the portal triad is a common strategy to minimize bleeding during liver transplantation. Increasing evidences suggests that oxygen derived free radicals and reintroduction of oxygen in ischemic tissue lead to ischemic and reperfusion injury (I/R) and lead to apoptosis and necrosis. Adult Wistar rat subjected to 60 min of partial liver ischemia followed by three hour reperfusion. Eighteen Wister rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion group (II) (n = 6), folic acid treated group (1 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n = 6). Apoptotic and necrotic hepatocytes, mitochondrial antioxidant enzymes were measured. Liver injury was assessed by alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology and electron microscopy. An ischemic and reperfusion hepatocellular injury was indicated by increased serum-ALT, AST, histopathology and electron microscopy studies. Apoptotic and necrotic cells were increased which was revealed by flow cytometry in I/R group. Pre- treatment with folic acid significantly decreased serum -ALT, AST levels, apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Histopathology and TEM studies showed markedly diminished hepatocellular injury in folic acid pretreated rats during the hepatic I/R, which reached a level comparable to saline-treated rat of sham operated group. On the basis of our findings it may be concluded that folic acid afforded significant protection from necrosis and apoptosis in I/R injury.

Development and evaluation of glyceryl behenate based solid lipid nanoparticles (SLNs) using hot self-nanoemulsification (SNE) technique

Negi, Jeetendra Singh,Chattopadhyay, Pronobesh,Sharma, Ashok Kumar,Ram, Veerma 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.3

The purpose of this research was to improve oral bioavailability of poorly aqueous soluble drug lopinavir using solid lipid nanoparticles (SLNs). Glyceryl behenate based SLNs of lopinavir were prepared using hot self-nanoemulsification (SNE) technique. The hot isotropic mixture of glyceryl behenate, Poloxamer 407 and polyethylene glycol 4000 was spontaneously self-nanoemulsify in hot water ($80^{\circ}C$) and SLNs were subsequently formed with rapid cooling. Hot SNE ability of isotropic mixture was visually assessed by ternary phase diagram study. Optimized SLNs were having particle size of $214.5{\pm}4.07nm$, entrapment efficiency of $81.6{\pm}2.3%$ and zeta potential of $-12.7{\pm}0.87mV$. SLNs were evaluated by transmission electron microscopy and atomic force microscopy for morphological details. Further, differential scanning calorimetry and x-ray diffraction were also performed for solid state characterization of SLNs. Higher oral bioavailability (3.56-fold) was found for lopinavir loaded SLNs in comparison to bulk lopinavir due to higher lymphatic drug transport (p<0.05). Results indicate that SLNs of glyceryl behenate can be successfully prepared by hot SNE technique.

Development and evaluation of glyceryl behenate based solid lipid nanoparticles (SLNs) using hot self-nanoemulsification (SNE) technique

Jeetendra Singh Negi,Pronobesh Chattopadhyay,Ashok Kumar Sharma,Veerma Ram 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.3

The purpose of this research was to improveoral bioavailability of poorly aqueous soluble drug lopinavirusing solid lipid nanoparticles (SLNs). Glyceryl behenatebased SLNs of lopinavir were prepared using hot selfnanoemulsification(SNE) technique. The hot isotropicmixture of glyceryl behenate, Poloxamer 407 and polyethyleneglycol 4000 was spontaneously self-nanoemulsify inhot water (80 C) and SLNs were subsequently formed withrapid cooling. Hot SNE ability of isotropic mixture wasvisually assessed by ternary phase diagram study. OptimizedSLNs were having particle size of 214.5 ± 4.07 nm,entrapment efficiency of 81.6 ± 2.3 % and zeta potential of-12.7 ± 0.87 mV. SLNs were evaluated by transmissionelectron microscopy and atomic force microscopy formorphological details. Further, differential scanning calorimetryand x-ray diffraction were also performed for solidstate characterization of SLNs. Higher oral bioavailability(3.56-fold) was found for lopinavir loaded SLNs in comparisonto bulk lopinavir due to higher lymphatic drugtransport (p\0.05). Results indicate that SLNs of glycerylbehenate can be successfully prepared by hot SNE technique.

Nanocurcumin–pyrroloquinoline formulation prevents hypertrophy–induced pathological damage by relieving mitochondrial stress in cardiomyocytes under hypoxic conditions

Sarita Nehra,Varun Bhardwaj,Anju Bansal,Pronobesh Chattopadhyay,Deepika Saraswat 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

This study investigates the therapeutic effect of a nanocurcumin formulation (NCF) containing nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) on ameliorating hypoxia-induced stress in hypertrophied primary human ventricular cardiomyocytes (HVCM) under hypoxic conditions, as validated in a Sprague-Dawley rat model of chronic hypobaric hypoxia (cHH)-induced right ventricular hypertrophy (RVH). Based on our previous findings, here, we analyzed the improvement in the protective efficacy of NCF against mitochondrial damage. The electron transport chain Complexes’ activities were analyzed as a chief operational center for mitochondrial homeostasis, along with key gene and protein markers for mitochondrial biogenesis, redox function, fatty acid oxidation, bio-energetic deficit and cell survival. NCF supplementation imparts cyto-protection from hypoxia-induced hypertrophy and damage in both in vitro and in vivo models while maintaining mitochondrial homeostasis better than NC and PQQ alone. This study proposes the use of NCF as a potential candidate molecule for imparting protection from high altitude-induced maladies in ascendants.

Assessment of physical stability and photoprotective activity of topical formulations added with calendula oil

Mishra, Arun K.,Mishra, Amrita,Chattopadhyay, Pronobesh 경희한의학연구센터 2012 Oriental Pharmacy and Experimental Medicine Vol.12 No.1

In the present work, the changes on physical properties (pH, viscosity, flow index and tixotropy) of topical formulations were evaluated following addition of calendula oil containing flavonoids. Also the photoprotective effect of these topical formulations were evaluated against ultra violet rays (UVR) induced sunburn in terms of sun protection factor (SPF). Formulation added with sun flower oil was used to compare the physical stability and photoprotective activity. Formulations added with calendula oil exhibited an average pH 7.2 and pseudoplastic behavior. The tixotropy values for formulations F3 and F4, after addition with calendula oil were found to be statistically decreased when compared with FS and Fb. The rheological parameters were constant during the study and the rheograms exhibited no sign of instability when studied at $4^{\circ}$, $27^{\circ}$ and $40^{\circ}C$ on different days of storage. The F3 and F4 samples showed statistically higher SPF (14 and 15 respectively) when compared with Fb (without active sunscreening agent). The highest SPF value 16 was recorded for FS (control formulation added with sun flower oil) while Fb showed lowest SPF vale 5.We concluded that F3, F4 and FS showed higher SPF and physical stability. This study of physical stability and photoprotectice activity of topical formulation can help in the development of sunscreen formulation.