The effect of emulgel preparation on the stability of Kojic acid in the topical anti-hyperpigmentation products.

BACKGROUND: The emulgel, a novel drug delivery system, merges emulsion and gel, offering advantages like enhanced stability, precise control over drug release kinetics, and increased drug absorption compared to emulsions alone. Kojic acid (KA) demonstrates potent inhibition of the tyrosinase enzyme, a crucial player in the melanin synthesis pathway. AIMS: The main objective of this experimental study is to formulate KA within an emulgel framework and assess its stability under various environmental conditions. METHODS: One percent of KA emulgel and 1% simple gel, serving as the control product, were supplemented with varying concentrations of sodium metabisulfite (SMBS) for its antioxidant properties. The formulations were segregated into four groups and subjected to diverse maintenance and stress conditions over a three-month period. Monthly evaluations of physicochemical alterations were conducted, initially employing digital photography, followed by the extraction of KA and subsequent quantification of its concentration through high performance liquid chromatography (HPLC). RESULTS: The best formulations for retaining KA among the prepared ones were the 0.25% SMBS KA emulgel and the 0.1% SMBS KA simple gel, capable of retaining 86% and 76% of the initial KA content under stress conditions, respectively (p < 0.0001). CONCLUSIONS: Regarding to this study, ideal storage condition for KA emulgel and simple gel is in the refrigerator temperatures. Moreover, optimal SMBS concentrations for stability enhancement are 0.25% for emulgel and 0.1% for the simple gel. A significant statistical difference was observed between refrigerated emulgel and simple gel in the retention of KA in the presence of optimum concentration of antioxidants (p < 0.0001).

Sodium metabisulfite as a cytotoxic food additive induces apoptosis in HFFF2 cells.

Sodium metabisulfite (SMB), an antioxidant agent, is extensively used as a preservative in food industry. The current study was aimed to clarify its potential toxic effects on human fetal foreskin fibroblasts (HFFF2) cells, in vitro. Subsequently, MTT results illustrated that exposure to SMB significantly (p < 0.0001) decreased HFFF2 cell viability in a dose-dependent manner, and the concentration of 25 µM reduced cell survival rates to 50% as the half-maximal inhibitory concentration of SMB. It was further shown that SMB exerted this cytotoxic effect on HFFF2 cells through apoptosis induction. qRT-PCR and western blotting results showed that treatment of HFFF2 cells with this food additive led to significant upregulation of Bax, caspase 8, and caspase 9 pro-apoptotic genes and downregulation of Bcl-2 expression as a pro-survival agent. Furthermore, SMB remarkably increased caspase 3 levels and promoted its activation through cleavage in treated cells. Besides, exposure to SMB increased ROS levels and activated autophagy in treated cells, which are considered as the other indicators for cell damage. Taken together, our findings suggested that SMB could exert remarkable toxic effects on human normal cells through multiple mechanisms, including apoptosis activation, and its widespread usage in food safety should be reconsidered.

Patch testing with sodium disulfite: North American Contact Dermatitis Group experience, 2017 to 2018.

BACKGROUND: Sodium disulfite (SD), also known as sodium metabisulfite, is an increasingly recognized cause of allergic contact dermatitis. OBJECTIVES: The objective of this work was to characterize individuals with positive patch test reactions to SD as well as analyse reaction strength, clinical relevance, and sources. METHODS: This is a retrospective analysis of patients patch tested with SD (1% petrolatum) by the North American Contact Dermatitis Group (NACDG), 2017 to 2018. RESULTS: Of 4885 patients patch tested with SD, 132 (2.7%) had a positive reaction. Common primary anatomic sites of dermatitis were face (28.8%), hands (20.5%), and a scattered/generalized distribution (13.6%). Compared with SD-negative patients, SD-positive patients were more likely male (odds ratio 2.81, 95% confidence interval 1.98-4.00) and/or over 40 years (odds ratio 1.95, 95% confidence interval 1.30-2.94). Reactions were most commonly + (50.4%) or ++ (34.1%); 65.2% were considered currently relevant. About 15.2% were definitively confirmed in sources, commonly personal care products (18.9%, especially hair dye), and drugs/medications/alcoholic beverages (9.1%). Only 2.3% of positive reactions were linked to occupation. CONCLUSIONS: Positive reactions to SD occurred in 2.7% of tested patients. Reactions were often clinically relevant and linked to personal care products and drugs/medications/alcoholic beverages.

Effects of deoxynivalenol and sodium meta-bisulphite on nutrient digestibility in growing pigs.

Deoxynivalenol (DON), a mycotoxin synthesised by the Fusarium, is known to affect the growth of pigs. This effect can be attenuated with sodium meta-bisulphite (SBS). The aim of this study was to evaluate the effect of SBS with antioxidant blend on nutrient digestibility in pigs fed a diet contaminated naturally with DON. Six crossbred castrated pigs fitted surgically with single-T cannulas in the distal ileum received one of four barley-corn-soybean diets with or without SBS. After 8 d of feeding, faeces and ileal digesta were collected for 2 d. Apparent ileal digestibility (AID) of the dry matter (DM), energy, nutrients and DON, and apparent total tract digestibility (ATTD) of DM, acid detergent fibre (ADF), neutral detergent fibre (NDF), energy and DON were evaluated. The AID of phosphorus, calcium and some amino acids was increased (p < 0.05) in the DON diets whereas the ATTD of DM and energy tended to decrease (p = 0.064 and p = 0.071). SBS reduced the AID of DM, energy, ADF, ether extract, phosphorus and DON (p < 0.05) but had no effect on the ATTD of DM, energy, fibre or DON. These results show that DON improved the AID of some nutrients but tended to reduce the ATTD of energy, which could explain, although anorexia is the main effect of DON on live weight gain, the reported negative effect of DON on pig growth. Finally, SBS with antioxidant blend had reduced AID of some nutrients and intestinal absorption of DON.

Sulfite concentration and the occurrence of headache in young adults: a prospective study.

BACKGROUND/OBJECTIVES: Sulfites are additives commonly used in food and wine industries that are associated to adverse clinical effects such as headaches. The objective of this study is to investigate the possible association between sulfite concentration in wine and the occurrence of headaches in young adults. SUBJECTS/METHODS: Eighty volunteers, aged between 18 and 25 years, were evaluated. Sub-groups (with or without previous headaches related with wine) were created and volunteers were submitted to two wine tests (minimum and maximum sulfite concentration accordingly to weight). A questionnaire was handed out after the test regarding the presence or not of headaches, their main characteristics, as well as other symptoms associated. RESULTS: Subjects that refer a previous headache history upon wine ingestion presented a risk 2266 greater of developing headaches after wine ingestion with a greater sulfite concentration. Those that refer constant headaches related to wine ingestion previous to the test present a risk of 6232 times more of developing headaches compared to those who refer sporadic headaches related to wine consumption. CONCLUSIONS: In our group of subjects, sulfite concentration in wine is related to the risk of developing headaches in individuals who are susceptible to wine induced headaches.

Dietary exposure to sulfites in Indonesians.

BACKGROUND AND OBJECTIVES: Information on dietary exposure to sulfites as preservative in consumer is needed as a scientific base for food safety policy making. The objective of this research was to conduct dietary exposure assessment to sulfites in consumers by using a deterministic method. METHODS AND STUDY DESIGN: The scope of work was identification of food products containing sulfites, determination of food consumption data from the individual food consumption survey report of 2014, determination of sulfite concentration in food, and calculation of sulfite exposure. RESULTS: 3,428 (9%) of 37,613 food products registered in National Agency of Drug and Food Control (2012-2015) may contain sulfite. The most used sulfite in food products was sodium metabisulfite. The mean of food containing sulfite consumption in all age groups was 131.4 g/person/day. The estimation of total exposure for all age groups were 0.27 mg/kgBW/day (38.6% ADI), 0.25 mg/kgBW/day (35.7% ADI) and 0.08 mg/kgBW/day (11.4% ADI) by using concentrations of Maximum Permitted Limit, reported maximum used level and reported maximum product test result, respectively. Food category contributed to the highest exposure in all age groups was spices, condiments, vinegar, powder or mixture for soups and broths, and other soy sauce category. CONCLUSIONS: The highest total exposure to sulfites was found in 0-59 month age group. The highest total exposure for the MPL (0.79 mg/kgBW/day) and the reported maximum used level (0.73 mg/kgBW/day) exceeded 112.9% ADI and 104.3% ADI, respectively while the exposure using reported maximum test result was still below ADI (0.25 mg/kgBW/day or 35.7% ADI).

Sodium houttuyfonate inhibits LPS­induced mastitis in mice via the NF­κB signalling pathway.

Sodium houttuyfonate (SH) has been indicated to play an important anti­inflammatory role. Previous studies have confirmed that SH can inhibit the NF­κB pathway in lipopolysaccharide (LPS)­induced mastitis in bovine mammary epithelial cells. However, the effects of SH on LPS­induced mastitis in animals should be verified to further evaluate its actual value. In the present study, the anti­inflammatory effects of SH were investigated in mouse models and a mouse mammary epithelial cell line. Hematoxylin and eosin staining (H&E) showed that SH therapy significantly alleviated the pathological changes in mammary glands. Myeloperoxidase (MPO) activity analysis demonstrated that SH substantially decreased MPO activity in vivo. RT­qPCR results showed that SH reduced the expression of interleukin (IL)­1, IL­6 and tumor necrosis factor α both in vivo and in vitro. In addition, western blot results indicated that SH suppressed the phosphorylation of nuclear factor kappa­light­chain­enhancer of activated B­cells (NF­κB) p65 protein and reduced the degradation of inhibitor of kappa light polypeptide gene enhancer in B­cells alpha protein in vivo and in vitro. These results demonstrated that SH ameliorates LPS­induced mastitis by inhibiting the NF­κB pathway.

Towards long-acting adrenaline for cardiopulmonary resuscitation: Production and characterization of a liposomal formulation.

The use of adrenaline in cardiopulmonary resuscitation is a long-standing medical procedure, recommended by several international guidelines. However, its unspecific action on adrenergic receptors and the need for repeated administrations pose serious concerns about its safety, the balance between benefits and risks being still under debate. To address this issue, a sustained release nano-formulation of adrenaline was developed. Adrenaline was encapsulated into PEGylated, anionic liposomes by a pH-driven loading technique. Particular attention was devoted to the prevention of oxidation of adrenaline by optimizing the preparative process and including an optimal amount of antioxidants in the formulation. The vesicles obtained were then characterized for size, zeta-potential, and lamellarity, while their morphology was described by cryo-TEM. The controlled release properties were confirmed by two different in vitro release-testing methods, and the biocompatibility was assayed on human endothelial cells in vitro.

In Vitro Analysis of the Degradation of Calcium Hydroxylapatite Dermal Filler: A Proof-of-Concept Study.

BACKGROUND: A dissolving agent for calcium hydroxylapatite (CaHA, Radiesse) soft-tissue filler would be of value should inadvertent intravascular injection, vascular compromise, nodule formation, or overcorrection occur. METHODS: In a prospective, single-center, proof-of-concept study, 12 cadaveric porcine skin samples were injected with CaHA (0.4-0.8 mL). Samples were then randomized to intralesional injection of 0.2-mL sodium thiosulfate (STS, 12.5 g/50 mL); 1 to 2 g of topical sodium metabisulfite (SMB, 25% SMB in 120-mL gel) applied with occlusion, or both intralesional STS and topical SMB. Control samples were not treated after CaHA injection. A 4-mm punch biopsy was obtained 24 hours after treatment, and tissue sections were stained with hematoxylin and eosin and prepared for light microscopy. A board-certified dermatopathologist estimated the amount of CaHA present in each sample. RESULTS: Intralesional STS alone or combined with topical SMB completely dissolved CaHA in the porcine skin samples. Topical SMB treatment reduced, but did not entirely clear CaHA from the tissue samples. The control samples contained easily identifiable CaHA microspheres. CONCLUSION: This proof-of-concept study illustrates the potential reversibility of CaHA filler with intralesional STS, topical SMB, and the combination of both agents. Larger, in vivo, studies are now warranted to provide further insight.

Hydrogen sulfide alleviates hyperhomocysteinemia-mediated skeletal muscle atrophy via mitigation of oxidative and endoplasmic reticulum stress injury.

Although hyperhomocysteinemia (HHcy) occurs because of the deficiency in cystathionine-ß-synthase (CBS) causing skeletal muscle dysfunction, it is still unclear whether this effect is mediated through oxidative stress, endoplasmic reticulum (ER) stress, or both. Nevertheless, there is no treatment option available to improve HHcy-mediated muscle injury. Hydrogen sulfide (H2S) is an antioxidant compound, and patients with CBS mutation do not produce H2S. In this study, we hypothesized that H2S mitigates HHcy-induced redox imbalance/ER stress during skeletal muscle atrophy via JNK phosphorylation. We used CBS+/- mice to study HHcy-mediated muscle atrophy, and treated them with sodium hydrogen sulfide (NaHS; an H2S donor). Proteins and mRNAs were examined by Western blots and quantitative PCR. Proinflammatory cytokines were also measured. Muscle mass and strength were studied via fatigue susceptibility test. Our data revealed that HHcy was detrimental to skeletal mass, particularly gastrocnemius and quadriceps muscle weight. We noticed that oxidative stress was reversed by NaHS in homocysteine (Hcy)-treated C2C12 cells. Interestingly, ER stress markers (GRP78, ATF6, pIRE1α, and pJNK) were elevated in vivo and in vitro, and NaHS mitigated these effects. Additionally, we observed that JNK phosphorylation was upregulated in C2C12 after Hcy treatment, but NaHS could not reduce this effect. Furthermore, inflammatory cytokines IL-6 and TNF-α were higher in plasma from CBS as compared with wild-type mice. FOXO1-mediated Atrogin-1 and MuRF-1 upregulation were attenuated by NaHS. Functional studies revealed that NaHS administration improved muscle fatigability in CBS+/- mice. In conclusion, our work provides evidence that NaHS is beneficial in mitigating HHcy-mediated skeletal injury incited by oxidative/ER stress responses.

Detoxification of Fusarium-contaminated maize with sodium sulphite - in vivo efficacy with special emphasis on mycotoxin residues and piglet health.

A feeding experiment with piglets was performed to examine the efficacy of a wet preservation of Fusarium (FUS)-contaminated maize with sodium sulphite (SoS) based on deoxynivalenol (DON) and zearalenone (ZEN) residue levels in urine, bile and liquor and health traits of piglets. For this purpose, 80 castrated male piglets (7.57 ± 0.92 kg BW) were assigned to four treatment groups: CON- (control diet, with 0.09 mg DON and <0.01 mg ZEN/kg diet), CON+ (diet CON-, wet-preserved with 5 g SoS/kg maize; containing 0.05 mg DON and <0.01 mg ZEN/kg diet), FUS- (diet with mycotoxin-contaminated maize; containing 5.36 mg DON and 0.29 mg ZEN/kg diet), and FUS+ (diet FUS-, wet-preserved with 5 g SoS/kg maize; resulting in 0.83 mg DON and 0.27 mg ZEN/kg diet). After 42 d, 40 piglets (n = 10 per group) were sampled. A clear reduction of DON levels by approximately 75% was detected in all specimens of pigs fed diet FUS+. ZEN was detected in all urine, bile and liquor samples, while their metabolites were only detectable in urine and bile. Additionally, their concentrations were not influenced by SoS treatment. Among the health-related traits, feeding of FUS diets increased the total counts of leukocytes and segmented neutrophil granulocytes irrespective of SoS treatment. SoS treatment increased the total blood protein content slightly with a similar numerical trend in albumin concentration. These effects occurred at an obviously lower level in FUS-fed groups. Moreover, SoS treatment recovered the reduction of NO production induced by feeding diet FUS- indicating an effect on the redox level. As this effect only occurred in group FUS+, it is obviously related to the adverse effects of the Fusarium toxins. In conclusion, treatment of FUS-contaminated maize with SoS decreased the inner exposure with DON as indicated by the lower DON levels in various piglet specimens. However, health-related traits did not consistently reflect this decreased exposure.

Effects of potential detoxifying agents on growth performance and deoxynivalenol (DON) urinary balance characteristics of nursery pigs fed DON-contaminated wheat.

Two experiments were conducted to evaluate potential detoxifying agents on growth of nursery pigs fed deoxynivalenol (DON)-contaminated diets. Naturally DON-contaminated wheat (6 mg/kg) was used to achieve desired DON levels. In a 21-d study, 238 pigs (13.4 ± 1.8 kg BW) were used in a completely randomized design with a 2 × 2 + 1 factorial arrangement. Diets were: 1) Positive control (PC; < 0.5 mg/kg DON), 2) PC + 1.0% Product V (Nutriquest LLC, Mason City, IA), 3) Negative control (NC; 4.0 mg/kg DON), 4) NC + 1.0% Product V, and 5) NC + 1.0% sodium metabisulfite (SMB; Samirian Chemicals, Campbell, CA). There were 6 or 7 replicate pens/treatment and 7 pigs/pen. Analyzed DON was decreased by 92% when pelleted with SMB, but otherwise matched formulated levels. Overall, a DON × Product V interaction was observed for ADG ( 0.05) with a tendency for an interaction for ADFI ( 0.10). As anticipated, DON reduced ( 0.001) ADG and ADFI, but the interaction was driven by even poorer growth when Product V was added to NC diets. Pigs fed NC diets had 10% poorer G:F ( 0.001) than PC-fed pigs. Reductions in ADG due to DON were most distinct (50%) during the initial period. Adding SMB to NC diets improved ( 0.01) ADG, ADFI, and G:F, and improved ( 0.02) ADG and G:F compared to the PC diet. A urinary balance study was conducted using diets 3 to 5 from Exp. 1 to evaluate Product V and SMB on DON urinary metabolism. A 10 d adaptation was followed by a 7 d collection using 24 barrows in a randomized complete block design. Pigs fed NC + SMB diet had greater urinary DON output ( 0.05) than pigs fed NC + Product V, with NC pigs intermediate. Daily DON excretion was lowest ( 0.05) in the NC + SMB pigs. However, degradation of DON-sulfonate back to the parent DON molecule was observed as pigs fed NC + SMB excreted more DON than they consumed (164% of daily DON intake), greater ( 0.001) than pigs fed the NC (59%) or NC + Product V (48%). Overall, Product V did not alleviate DON effects on growth nor did it reduce DON absorption and excretion. However, hydrothermally processing DON-contaminated diets with 1.0% SMB restored ADFI and improved G:F. Even so, the urinary balance experiment revealed that some of the converted DON-sulfonate can degrade back to DON under physiological conditions. While further research is needed to discern the stability of the DON-sulfonate, SMB appears promising to restore performance in pelleted DON-contaminated diets.

Gastric mucosal irritation following oral exposure to sodium metabisulphite: A reproducible effect?

Sulphiting agents, such as sodium metabisulphite (SM), are used in food as bleaching agents and to prevent browning reactions. A 1972 repeat dose study in rats found that dietary sulphites caused irritation of the stomach with inflammation, hyperplasia and bleeding. We conducted a 7-day dietary study in rats to confirm that stomach lesions were the most sensitive toxicological endpoint. Rat feed was prepared daily with 0%, 0.25%, 0.5%, 1% or 4% (w/w) SM. Parameters included clinical signs, feed and water intake, bodyweight gain, haematology, serum protein chemistry, necropsy findings and gastrointestinal histopathology. There were no treatment-related clinical signs or gastrointestinal lesions. Mean bodyweight gain was markedly decreased in the 4% (w/w) SM group although feed consumption was marginally depressed. Slightly lower mean values for RBC, Hb, Hct, total WBC and lymphocyte count were observed in the 4% SM group with no evidence of compensatory haematopoiesis. The gastric lesions in rats observed in a 1972 study of dietary SM for 10-56 days could not be replicated. These findings create uncertainty around the most relevant toxicological endpoint to establish a suitable health based guidance value, which can only be overcome if a robust long-term dietary study is undertaken.

Topical sodium metabisulfite for the treatment of calcinosis cutis: a promising new therapy.

Calcinosis cutis is a chronic calcium-mediated disease that causes significant morbidity. Multiple treatments have been tried, with varying results; indeed, to date, no standard treatment has been generally accepted. Sodium metabisulfite is an inorganic compound that, when it reacts with oxygen, becomes sodium sulfate, a metabolite of sodium thiosulfate that has a similar ability to inhibit calcium oxalate agglomeration. Four women diagnosed with calcinosis cutis, secondary to dermatomyositis, systemic sclerosis and radiodermatitis after breast cancer, were evaluated for their response to topical 25% sodium metabisulfite. In all patients a decrease in lesion size, erythema and pain from injuries was shown, with complete resolution of the associated ulcers. One patient had a complete response. None experienced adverse effects. Topical sodium metabisulfite is a promising emerging therapy that should be considered as a valid alternative treatment in calcinosis cutis. Randomized prospective studies are required to evaluate its true efficacy.

Contact dermatitis in patients undergoing serial intravitreal injections.

BACKGROUND: Anti-vascular endothelial growth factor (VEGF) medication, injected intravitreally, is currently the standard of care in patients with different retinal pathologies. Since its introduction in 2006, an increasing number of patients have undergone this procedure in Ghent University Hospital. Strikingly, more patients were diagnosed with contact dermatitis caused by ophthalmic products used during intravitreal injection procedure. OBJECTIVES: To identify which of the substances used during intravitreal injection is most likely to cause contact dermatitis. PATIENTS/MATERIALS/METHODS: Sixteen patients who developed a burning and stinging sensation and swelling of the eyelids after intravitreal injection were tested. All patients were patch tested with the Belgian baseline series, as well as a cosmetic, a pharmaceutical and an ophthalmic series, including the different eye drops used during the intravitreal injection procedure. RESULTS: Fourteen of 16 patients reacted to at least one of the substances used during the injection procedure. Nine patients reacted to phenylephrine (56%), 5 to iso-Betadine(®) ophthalmic solution (31%), and 3 patients to sodium metabisulfite (16%). CONCLUSIONS: The most common causal allergen was phenylephrine, being positive in 56% of patients. Patients most likely become sensitized because of the high frequency of usage of phenylephrine during repeated intravitreal injections and follow-up consultations.

Effect of sodium houttuyfonate on symptom pattern of lung-Qi deficiency in rats induced by bacterialbiofilm infection.

OBJECTIVE: To investigate the in vivo inhibitory effects of sodium houttuyfonate (SH) on symptom pattern of Qi-deficiency in rats induced by infection of bacterial biofilm on rat respiratory tract. METHODS: Symptom pattern is a term used in Traditional Chinese Medicine (TCM) to define a cluster of symptoms in a medical condition. Based on the pattern, TCM therapies are administered. The symptom pattern used in this study was lung-Qi deficiency pattern identified in rats, which was induced by nasal intubation drip of Pseudomonas aeruginosa (P. aeruginosa) (two strains) to form bacterial biofilm on airway combined with stimulation of cold and fatigue. We measured the variations of the symptoms of the pattern, weight, spleen and thymus index, blood gas, lung bronchial tissue pathology and cytokine of rat in different treatments and control groups. RESULTS: The rats of SH-treatment groups had not showed typical symptoms comparing with model group in the early stage of infection. The weight, spleen and thymus index of the SH-treatment groups were significantly higher comparing with untreated model group. The SH-treatment groups also showed higher O(2) partial pressure and lower CO(2) partial pressure than model group. Furthermore, we found that the bronchopulmonary section of SH-treatment groups not showed typical pathogenic variation in model group. The comparison of cytokine concentration in different groups indicated that SH could prevent the over-production of cytokine to reduce the inflammation occurrence. CONCLUSION: In the early stage of airway infection by biofilm of P. aeruginosa, application of SH can prevent the occurrence of lung-Qi deficiency pattern.

Proteomic identification of mitochondrial targets involved in andrographolide sodium bisulfite-induced nephrotoxicity in a rat model.

Our previous works have indicated that the mitochondrion is the primary target of nephrotoxicity induced by andrographolide sodium bisulfate (ASB), but the mechanisms of ASB-induced nephrotoxicity have remained largely unknown. In this study, proteomic analysis was used to explore the changes in the renal mitochondrial proteome in SD rats after treatment with ASB. SD rats were intraperitoneally administered with ASB (100, 600mg/kg/d) for 7 days. Renal impairment was evaluated by pathological observation. Two-dimensional gel electrophoresis (2-DE), as well as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS), was applied for the identification of mitochondrial protein and was validated by Western blotting. Protein-protein interactions were analyzed using a Web-based bioinformatics tool (STRING, version 9.1). Rat kidneys exhibited histopathological changes after treatment with ASB, and 13 proteins were significantly changed, including ES1 protein homolog, heat shock cognate 71kDa protein, peroxiredoxin-1 (Prdx1), cytochrome C oxidase subunit 5B (COX5B), prohibitin (PHB), threonine-tRNA ligase, pyruvate dehydrogenase E1 component subunit beta (PDH-ß), voltage-dependent anion-selective channel protein 2 (VDAC2), voltage-dependent anion-selective channel protein 1 (VDAC1), adenylate kinase 2 (KAD2) and others. These data demonstrated that the expression levels of several proteins significantly changed in the mitochondria, and these proteins could be candidate biomarkers for ASB-induced nephrotoxicity.