Comparison of urine proteome among rat models by intraperitoneal injection with single bacteria and co-injection with two bacteria.

PURPOSE: To explore and compare urine proteome changes among rat models by intraperitoneal injection with single bacteria and co-injection with two bacteria. METHOD: Escherichia coli and Staphylococcus aureus are two common human pathogens. Three rat models were established: (i) the intraperitoneal co-injection of E. coli and S. aureus model (ES model), (ii) intraperitoneal injection of E. coli model (E model), and (iii) intraperitoneal injection of S. aureus model (S model). Urinary proteomes on days 0, 1 and 2 of the three models were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RESULTS: A total of 111, 34 and 94 differential proteins were identified in the ES model, E model and S model, respectively. Among them, some differential proteins were reported to be associated with bacterial infection. Approximately 47% differential proteins in the E model overlapped with ES model, and 37% differential proteins in the S model overlapped with ES model. Compared with the E model and S model, a total of 71 unique differential proteins were identified in the ES model. CONCLUSION: Our results indicated that (1) the urine proteome could distinguish different bacterial intraperitoneal injections models and (2) the effects of co-injection with two bacteria on the urine proteome were not simple superposition of single injection.

Development of a rat capnoperitoneum phantom to study drug aerosol deposition in the context of anticancer research on peritoneal carcinomatosis.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a promising approach with a high optimization potential for the treatment of peritoneal carcinomatosis. To study the efficacy of PIPAC and drugs, first rodent cancer models were developed. But inefficient drug aerosol supply and knowledge gaps concerning spatial drug distribution can limit the results based on such models. To study drug aerosol supply/deposition, computed tomography scans of a rat capnoperitoneum were used to deduce a virtual and a physical phantom of the rat capnoperitoneum (RCP). RCP qualification was performed for a specific PIPAC method, where the capnoperitoneum is continuously purged by the drug aerosol. In this context, also in-silico analyses by computational fluid dynamic modelling were conducted on the virtual RCP. The physical RCP was used for ex-vivo granulometric analyses concerning drug deposition. Results of RCP qualification show that aerosol deposition in a continuous purged rat capnoperitoneum depends strongly on the position of the inlet and outlet port. Moreover, it could be shown that the droplet size and charge condition of the drug aerosol define the deposition efficiency. In summary, the developed virtual and physical RCP enables detailed in-silico and ex-vivo analyses on drug supply/deposition in rodents.

Injection of Escherichia coli to Induce Sepsis.

Mouse models of bacterial sepsis are widely used in research to investigate the underlying molecular mechanisms of sepsis and to develop clinically useful therapeutic regimens. Three commonly used mouse sepsis models include (a) injection of bacterial endotoxin, (b) infusion of cultured bacteria, and (c) cecal ligation and puncture. Here we describe the induction of bacterial sepsis in mice by intraperitoneal injection of cultured live Escherichia coli cells. The severity of the sepsis can be regulated by the number of E. coli cells injected into the peritoneal cavity of mice.

Pharmacokinetic Advantage of ASD Device Promote Drug Absorption through the Epicardium.

PURPOSE: Due to low therapeutic efficacy and severe adverse reaction of systemic administration for coronary heart disease (CHD) therapy, we designed a novel local target delivery system, called Active hydraulic ventricular Support Drug delivery system (ASD). This study aims to investigate the potential advantages of ASD compared to intrapericardial (IPC) injection and factors affecting drug absorption through epicardium. METHODS: Liposoluble, water soluble and viscous solutions of cyanine 5 (Cy5) fluorescent dye were delivered individually through ASD and IPC in Sprague-Dawley (SD) rats and then tissues were isolated and observed by in vivo imaging system. Atria and ventricles of the heart were taken for the paraffin section and observed under a fluorescence microscope. RESULTS: The fluorescence intensity of Cy5 injected by ASD distributed in the heart was significantly higher than IPC injection. Whereas, the fluorescence signal spread in other tissues such as lung, liver, spleen, and kidney of ASD groups was much weaker. Moreover, when choosing liposoluble and viscous Cy5, the intensity of the heart turned stronger and fluorescence dye distributed in other tissues was lesser. CONCLUSIONS: The application of ASD device may provide a promising route of drug delivery for CHD. Furthermore, increasing viscosity of the solution and liposolublity of the drug was beneficial to facilitate drug absorption through the epicardium.

Intraperitoneal and subcutaneous glucagon delivery in anaesthetized pigs: effects on circulating glucagon and glucose levels.

Glucagon is a pancreatic hormone and increases the blood glucose levels. It may be incorporated in a dual hormone artificial pancreas, a device to automatically and continuously control blood glucose levels of individuals with diabetes. Artificial pancreas systems have been developed for use in the subcutaneous tissue; however, the systems are not fully automated due to slow dynamics. The intraperitoneal space is therefore investigated as an alternative location for an artificial pancreas. Glucose dynamics after subcutaneous and intraperitoneal glucagon delivery in ten anaesthetized pigs were investigated. The pigs received intraperitoneal boluses of 0.3 µg/kg and 0.6 µg/kg and a subcutaneous bolus of 0.6 µg/kg in randomized order. They also received an intraperitoneal bolus of 1 mg given at the end of the experiments to test the remaining capacity of rapid glucose release. Six pigs were included in the statistical analysis. The intraperitoneal glucagon bolus of 0.6 µg/kg gave a significantly higher glucose response from 14 to 30 min compared with the subcutaneous bolus. The results indicate that glucagon induces a larger glucose response after intraperitoneal delivery compared with subcutaneous delivery and is encouraging for the incorporation of glucagon in an intraperitoneal artificial pancreas.

Restricted access to innovative surgical technique related to a specific training, is it ethical? Example of the PIPAC procedure. A systematic review and an experts survey.

OBJECTIVE: Using the example of Pressurized Intra Peritoneal Aerosol Chemotherapy (PIPAC), we analyse the development model of this procedure and provide an ethical analysis of the involvement of the industry in a new development. SUMMARY BACKGROUND DATA: In the case of breakthrough innovation, medical training is essential for safe use of the new procedure. In some cases, pharmaceutical companies decide to organise this training. But when it becomes the only training opportunity to use the device, scientists and clinicians could be exposed to a conflict of interest? METHODS: We performed a literature review of PIPAC publications using the STROBE criteria. Then, we conducted interviews with an expert panel to analyse the ethical impact of involvement of the industry in the development of the PIPAC procedure. RESULTS: The number of publications has increased every year since the first publication in Germany, where the technology was developed in 2013. The scientific production was of good quality, with a mean STROBE score of 18.2 ± 2.4 out of 22 points. Ten of the 33 included studies declared a conflict of interest. From the interviews, the main axe concerning the implication of the industry was the training model. The company had decided that only trained and approval surgeon could perform the PIPAC procedure. All four interviewed practitioners agreed that it was initially a good way to implement the procedure safely, but later they felt uncomfortable about the control and validation by the industry. CONCLUSION: Based on the growing number of published papers from a growing number of international centres, the controlled training model is not limiting. However, the different levels of conflict of interest complicate transparency, and we postulated that this development model is limited to the beginning of the procedure diffusion. CLINICALTRIAL. GOV REGISTRATION: NCT04341337.

Intraperitoneal injection of IFN-γ restores microglial autophagy, promotes amyloid-ß clearance and improves cognition in APP/PS1 mice.

Autophagy is a major self-degradative process that maintains cellular homeostasis and function in mammalian cells. Autophagic dysfunction occurs in the early pathogenesis of Alzheimer's disease (AD) and directly regulates amyloid-ß (Aß) metabolism. Although it has been proven that the cytokine IFN-γ enhances autophagy in macrophage cell lines, whether the signaling cascade is implicated in Aß degradation in AD mouse models remains to be elucidated. Here, we found that 9 days of the intraperitoneal administration of IFN-γ significantly increased the LC3II/I ratio and decreased the level of p62 in APP/PS1 mice, an AD mouse model. In vitro, IFN-γ protected BV2 cells from Aß toxicity by upregulating the expressions of Atg7 and Atg5 and the LC3II/I ratio, whereas these protective effects were ablated by interference with Atg5 expression. Moreover, IFN-γ enhanced autophagic flux, probably through suppressing the AKT/mTOR pathway both in vivo and in vitro. Importantly, using intravital two-photon microscopy and fluorescence staining, we found that microglia interacted with exogenous IFN-γ and Aß, and surrounded Aß in APP/PS1;CX3CR1-GFP+/- mice. In addition, IFN-γ treatment decreased the Aß plaque load in the cortex and hippocampus and rescued cognitive deficits in APP/PS1 mice. Our data suggest a possible mechanism by which the peripheral injection of IFN-γ restores microglial autophagy to induce the phagocytosis of cerebral Aß, which represents a potential therapeutic approach for the use of exogenous IFN-γ in AD.

Mth1 deficiency provides longer survival upon intraperitoneal crocidolite injection in female mice.

Exposure to asbestos fiber is central to mesothelial carcinogenesis. Recent sequencing studies on human and rodent malignant mesothelioma (MM) revealed frequently mutated genes, including CDKN2A, BAP1 and NF2. Crocidolite directly or indirectly catalyses the generation of hydroxyl radicals, which appears to be the major driving force for mesothelial mutations. DNA base modification is an oxidative DNA damage mechanism, where 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the most abundant modification both physiologically and pathologically. Multiple distinct mechanisms work together to decrease the genomic level of 8-OHdG through the enzymatic activities of Mutyh, Ogg1 and Mth1. Knockout of one or multiple enzymes is not lethal but increases the incidence of tumors. Here, we used single knockout (KO) mice to test whether the deficiency of these three genes affects the incidence and prognosis of asbestos-induced MM. Intraperitoneal injection of 3 mg crocidolite induced MM at a fraction of 14.8% (4/27) in Mth1 KO, 41.4% (12/29) in Mutyh KO and 24.0% (6/25) in Ogg1 KO mice, whereas 31.7% (20/63) induction was observed in C57BL/6 wild-type (Wt) mice. The lifespan of female Mth1 KO mice was longer than that of female Wt mice (p = 0.0468). Whole genome scanning of MM with array-based comparative genomic hybridization revealed rare genomic alterations compared to MM in rats and humans. These results indicate that neither Mutyh deficiency nor Ogg1 deficiency promotes crocidolite-induced MM in mice, but the sanitizing nucleotide pool with Mth1 is advantageous in crocidolite-induced mesothelial carcinogenesis.

The Glucose Tolerance Test in Mice.

Type 2 diabetes is characterized by glucose intolerance, caused by insulin resistance in peripheral metabolic tissues and by impaired glucose-stimulated insulin secretion, the hallmark of beta-cell dysfunction. The glucose tolerance test is used in clinic and research to identify individuals with impaired glucose tolerance and overt type 2 diabetes. It is the most routinely used physiological test for first pass assessment of glucose homeostasis in rodents because of its simplicity. The GTT measures changes in blood glucose concentration over a 2-h period following the administration of a bolus of glucose. However, this simplicity belies several important considerations which need to be addressed, to aid reproducibility and produce interpretable data. Here, we describe in detail how to perform a GTT using four different routes of glucose administration: intraperitoneal, oral, voluntary oral, and intravenous.

Assessment of Insulin Tolerance In Vivo in Mice.

Insulin resistance in humans and mice is an important hallmark of metabolic diseases. Therefore, assessment of insulin sensitivity/resistance in animal models provides valuable information in the pathophysiology of diabetes and obesity. Depending on the nature of the information required, we can choose between direct and indirect techniques available for the determination of insulin sensitivity. Thus, the complex hyperinsulinemic-euglycemic glucose clamps and the insulin suppression test assess insulin-mediated glucose utilization under steady-state conditions, whereas less complex methods, such as the insulin tolerance test (ITT), rely on measurements of blood glucose levels in animals subjected to intraperitoneal insulin loading. Finally, surrogated indexes derived from blood glucose and plasma insulin levels are also available for assessment of insulin sensitivity/resistance in vivo. In this chapter, we focus on the intraperitoneal insulin tolerance test (IPITT) protocol for measuring insulin resistance in mice.

Intraperitoneal administration of biocompatible hyaluronic acid hydrogel containing multi-chemotherapeutic agents for treatment of colorectal peritoneal carcinomatosis.

Colorectal peritoneal carcinomatosis (CRPC) is an advanced stage of colorectal cancer (CRC), which significantly decreases patient survival and quality of life. Here, the naturally occurring polysaccharide hyaluronic acid (HA) was used to prepare an injectable hydrogel and simultaneously deliver 5-fluorouracil (5-FU), cisplatin (DDP) and paclitaxel (PTX) microspheres for intraperitoneal CRPC chemotherapy. The drug-loaded HA hydrogel released the drugs in a sustained manner, and showed low toxicity both in vitro and in a mouse model of CRPC. Furthermore, direct injection of the drug-loaded HA hydrogel in the abdominal cavity of tumor-bearing mice significantly decreased tumor growth and liver/lung metastasis, along with decreasing the volume of ascites and inhibiting local intestinal infiltration of the tumor cells. Therefore, this novel multi-drug hydrogel delivery system may effectively clear CRPC tumors without any adverse effects when used in intraperitoneal chemotherapy.

Intraperitoneal injection of ginkgolide B, a major active compound of Ginkgo biloba, dose-dependently increases the amount of wake and decreases non-rapid eye movement sleep in C57BL/6 mice.

The terpene lactones of Ginkgo biloba extract, namely ginkgolides (A, B, and C) and bilobalide, possess antioxidant, anti-inflammatory, and neuroprotective effects. They are widely prescribed for the treatment of cerebral dysfunctions and neurological impairments. In addition, they demonstrate antagonistic action at the gamma-aminobutyric acid type A and glycine receptors, which are members of the ligand-gated ion channel superfamily. In the present study, the effects of ginkgolides (A, B, and C) and bilobalide on sleep in C57BL/6 mice were investigated. Ginkgolide B was found to dose-dependently increase the amount of wake and decrease that of non-rapid eye movement sleep without changes in the electroencephalography power density of each sleep/wake stage, core body temperature and locomotor activity for the first 6 h after intraperitoneal injection. Of note, the amount of wake after injection of 5 mg/kg of ginkgolide B showed a significant increase (14.9 %) compared with that of vehicle (P = 0.005). In contrast, there were no significant differences in the amount of sleep, core body temperature, and locomotor activity in the mice injected with ginkgolide A and C. Bilobalide briefly induced a decrease in locomotor activity but did not exert significant effects on the amounts of sleep and wake. The modes of action of the wake-enhancing effects of ginkgolide B are unknown. However, it may act through the antagonism of gamma-aminobutyric acid type A and glycine receptors because it is established that these inhibitory amino acids mediate sleep and sleep-related physiology. It is of interest to further evaluate the stimulant and awaking actions of ginkgolide B on the central nervous system in clinical and basic research studies.

Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies?

Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. While this route is an easy to master, quick, suitable for chronic treatments and with low impact of stress on laboratory rodents, there is a common concern that it may not be an acceptable route for drug administration in experimental studies. The latter is likely due to sparsity of information regarding pharmacokinetics of pharmacological agents and the mechanisms through which agents get systemic exposure after IP administration. In this review, we summarize the main mechanisms involved in bioavailability of IP administered drugs and provide examples of pharmacokinetic profiles for small and large molecules in comparison to other routes of administration. We conclude with a notion that IP administration of drugs in experimental studies involving rodents is a justifiable route for pharmacological and proof-of-concept studies where the goal is to evaluate the effect(s) of target engagement rather than properties of a drug formulation and/or its pharmacokinetics for clinical translation.

A resistance-sensing mechanical injector for the precise delivery of liquids to target tissue.

The precision of the delivery of therapeutics to the desired injection site by syringes and hollow needles typically depends on the operator. Here, we introduce a highly sensitive, completely mechanical and cost-effective injector for targeting tissue reliably and precisely. As the operator pushes the syringe plunger, the injector senses the loss-of-resistance on encountering a softer tissue or a cavity, stops advancing the needle and delivers the payload. We demonstrate that the injector can reliably deliver liquids to the suprachoroidal space-a challenging injection site that provides access to the back of the eye-for a wide range of eye sizes, scleral thicknesses and intraocular pressures, and target sites relevant for epidural injections, subcutaneous injections and intraperitoneal access. The design of this simple and effective injector can be adapted for a broad variety of clinical applications.

Assessment of the aerosol distribution pattern of a single-port device for intraperitoneal administration of therapeutic substances.

BACKGROUND: In the last 20 years, intraperitoneal chemotherapy (IPC) has been explored as a modality for the management of peritoneal metastases of gynecologic, gastrointestinal, and primary peritoneal tumors. Direct delivery of chemotherapeutic agents to the peritoneal cavity space has proved superior to systemic chemotherapy when evaluating characteristics such as drug concentration reached in the peritoneal space, penetration into peritoneal metastases, and chemotherapy-related toxicity. Traditionally, IPC is delivered by peritoneal lavage with a liquid solution. This form of delivery has limitations, including inhomogeneous intraperitoneal distribution and limited ability to penetrate tissues and metastatic nodules. An alternative mode of delivery is so-called pressurized intraperitoneal aerosol chemotherapy (PIPAC). Within this context, the present study sought to identify the pattern of spatial distribution of therapeutic solutions aerosolized into the peritoneal space using a single-port PIPAC device and ascertain whether the aerosolized method is superior to the traditional (liquid) mode of IPC delivery. METHODS: Analysis of the rate of intra-abdominal staining with aerosolized 2% silver nitrate in five porcine models. RESULTS: Assessment of differences in stain impregnation between the upper, middle, and lower abdomen did not reveal significant differences (p = 0.42). The median sum scores were 1 for the upper abdomen and 3 for the middle and lower abdomen. CONCLUSIONS: Aerosolization does not reach all regions of the abdomen homogeneously. However, adequate exposure of the upper abdomen, mid-abdomen, and lower abdomen to chemotherapeutic agents can be achieved with PIPAC.

MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats.

Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 µg/mL MWCNT-7 or 0.250 µg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.

Oxytocin delivered nasally or intraperitoneally reaches the brain and plasma of normal and oxytocin knockout mice.

Intranasal delivery of oxytocin (Oxt) has been identified as a potential therapeutic to target human conditions characterized by social deficits, yet the ability of this administrative route to deliver to the brain is unconfirmed. Oxt knockout (Oxt KO) and wildtype C57BL/6 J male mice received Oxt (12 µg total amount) either by nasal or intraperitoneal administration. Oxt concentrations were monitored for 2 h after administration in circulation via a jugular vein catheter and in the brain by two intracerebral microdialysis probes. Group sizes varied from 4 to 7 mice (n = 22 total). We document for the first time that Oxt applied to the nasal mucosa after nasal administration is delivered to the extracellular fluid in the brain. After nasal application, Oxt concentrations in circulation and in the extracellular fluid of the amygdala and, to an extent, the dorsal hippocampus, rose within the first 30 min and remained elevated for the subsequent hour. These findings were confirmed in an Oxt KO mouse line, establishing that the circulating and brain Oxt elevations derive from the administered dose. Interestingly, the pharmacokinetics of Oxt were slightly biased to the brain after nasal administration and to the periphery following intraperitoneal injection. No change in vasopressin levels was detected. These findings have stimulating implications for the interpretation of various behavioral and physiological effects described in animal and human studies after nasal administration of Oxt and provide the pharmacokinetics necessary to develop this drug delivery route for therapeutic purposes.

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC).

BACKGROUND: pressurized intraperitoneal aerosol chemotherapy (PIPAC), with or without electrostatic precipitation (ePIPAC), was recently introduced in the treatment of peritoneal metastases (PM) from ovarian cancer (OC). Preliminary clinical data are promising, but several methodological issues as well the anticancer efficacy of PIPAC remain unaddressed. Here, we propose a rat ePIPAC model that allows to study these issues in a clinically relevant, reproducible, and high throughput model. METHODS: laparoscopy and PIPAC were established in healthy Wistar rats. Aerosol properties were measured using laser diffraction spectrometry based granulometric analyses. Electrostatic precipitation was accomplished using a commercially available generator (Ultravision™). A xenograft model of ovarian PM was created in athymic rats using intraperitoneal (IP) injection of SKOV-3 luciferase positive cells. Tumor growth was monitored weekly by in vivo bioluminescence imaging. RESULTS: PIPAC and electrostatic precipitation were well tolerated using a capnoperitoneum of 8 mmHg. All rats survived the (e)PIPAC procedure and no gas or aerosol leakage was observed over the entire procedure. With an injection pressure of 20 bar, granulometry showed a mean droplet diameter (D(v,0.5)) of 47 µm with a flow rate of 0.5 mL/s, and a significantly lower diameter (30 µm) when a flow rate of 0.8 mL/s was used. Experiments using IP injection of SKOV-3 luciferase positive cells showed that after IP injection of 20 × 106 cells, miliary PM was observed in all animals. PIPAC was feasible and well supported in these tumor bearing animals. CONCLUSIONS: we propose a reproducible and efficient rodent model to study PIPAC and ePIPAC in OC xenografts with widespread PM. This model allows to characterize and optimize pharmacokinetic and biophysical parameters, and to evaluate the anti-cancer efficacy of (e)PIPAC treatment.

A Protocol to Perform Systemic Lipopolysacharide (LPS) Challenge in Rats / Protocolo para realizar reto sistémico con lipopolisacárido (LPS) en ratas

Abstract 19. Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria. In animals, intraperitoneal administration of LPS, stimulates innate immunity and the production of proinflammatory cytokines. LPS provides an inflammatory stimulus that activates the neuroimmune and neuroendocrine systems resulting in a set of responses termed sickness behavior. The purpose of this protocol is to describe step-by-step the preparation and procedure of application of intraperitoneal injection of LPS in rats, as a guide for those researchers that want to use this assay to mount an inflammatory response. LPS intraperitoneal challenge in rats has been widely used to evaluate antiinflammatory reagents and to address basic scientific questions.

Resumen 23. El lipopolisacárido (LPS) es un componente de la membrana externa de las bacterias Gram negativas. En animales, la administración intraperitoneal de LPS estimula la inmunidad innata y la producción de citoquinas proinflamatorias. El LPS proporciona un estímulo inflamatorio que activa el sistema neuroinmunológico y el sistema neuroendocrino, lo que da como resultado un conjunto de respuestas denominadas conductas de enfermedad. El propósito de este protocolo es describir paso a paso la preparación y el procedimiento de aplicación de la inyección intraperitoneal de LPS en ratas, como una guía para aquellos investigadores que desean utilizar este método para estimular una respuesta inflamatoria en el animal. La estimulación con LPS en ratas, aplicada intraperitonealmente, se ha utilizado ampliamente para evaluar reactivos antiinflamatorios y para abordar preguntas básicas de investigación científica.

Intraperitoneal Injection of Acetate Protects Mice Against Lipopolysaccharide (LPS)­Induced Acute Lung Injury Through Its Anti-Inflammatory and Anti-Oxidative Ability.

BACKGROUND As a member of short-chain fatty acids, acetate exhibits anti-inflammatory capacity. The present study aimed to investigate the effect of acetate on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explored its underlying mechanism. MATERIAL AND METHODS Acetate (250 mM, 400 µL) was given intraperitoneally 30 minutes after LPS (5 mg/kg) intratracheal injection. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected 6 hours after the challenge of LPS. The histopathology scores, wet-to-dry weight ratios, protein content, and cytokine levels in BALF were assessed. RESULTS The acetate treatment resulted in improved lung pathological score, alleviated LPS-induced microvascular permeability, and suppressed the production of reactive oxygen species. Furthermore, acetate decreased the level of pro-inflammatory cytokines and chemokines in the lungs and BALF, consistent with the declined immune cell counting found in BALF. In addition, phosphorylation levels of mitogen-activated protein kinase (MAPK) pathway in lung tissues were downregulated by acetate. CONCLUSIONS These results suggested that acetate exerts its protective effects via anti-inflammatory and anti-oxidant activities on LPS-induced ALI.