title: Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load.
abstract: Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro-inflammatory cytokines (IL-1β and TNFα) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Soumen
authors.initials: S
authors.lastname: Choudhury
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Kannan
authors.initials: K
authors.lastname: Kandasamy
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Bhojane Somnath
authors.initials: BS
authors.lastname: Maruti
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: M Pule
authors.initials: MP
authors.lastname: Addison
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Jaya Kiran
authors.initials: JK
authors.lastname: Kasa
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Sazad A
authors.initials: SA
authors.lastname: Darzi
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Thakur Uttam
authors.initials: TU
authors.lastname: Singh
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Subhashree
authors.initials: S
authors.lastname: Parida
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Jeevan Ranjan
authors.initials: JR
authors.lastname: Dash
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Vishakha
authors.initials: V
authors.lastname: Singh
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India. Electronic address: smishraivri@rediffmail.com.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Mishra
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D000818:Animals; D000069059:Atorvastatin / Q000008:administration & dosage*; D058491:Bacterial Load / Q000187:drug effects* / Q000502:physiology; D004359:Drug Therapy, Combination; D015378:Imipenem / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology
chemical_list: D018836:Inflammation Mediators; D015378:Imipenem; D000069059:Atorvastatin
keywords: Atorvastatin; Imipenem; Lung injury; Sepsis