Clinical and genetic analysis of essential hypertension with CYB gene m.15024G>A mutation / 浙江大学学报·医学版

OBJECTIVES@#To explore the role of mitochondrial CYB 15024G>A mutation in the development of essential hypertension.@*METHODS@#Mitochondrial genome sequences of hypertensive patients were obtained from previous studies. Clinical and genetic data of a hypertensive patient with mitochondrial CYB 15024G>A mutation and its pedigree were analyzed. Lymphocytes derived from patient and family members were transformed into immortalized lymphoblastoid cell lines, and the levels of adenosine triphosphate (ATP), mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were detected.@*RESULTS@#The penetrance of this essential hypertension family was 42.9%, and the age of onset was 46-68 years old. Mitochondrial genome sequencing results showed that all maternal members carried a highly conserved mitochondrial CYB 15024G>A mutation. This mutation could affect the free energy of mitochondrial CYB for secondary and tertiary structure and protein folding, thereby changing its structural stability and the structure of the electron transfer function area around the mutation site. Compared with the control, the cell line carrying the mitochondrial CYB 15024G>A mutation showed significantly decreased levels of mitochondrial CYB, ATP and mitochondrial membrane potential, and increased levels of ROS (P<0.01).@*CONCLUSIONS@#Mitochondrial CYB 15024G>A mutation may affect the structure of respiratory chain subunits and mitochondrial function, leading to cell dysfunction, which suggests that the mutation may play a synergistic role in essential hypertension.

Mitochondrial dysfunction in neural tube defects / 国际儿科学杂志

Neural tube defects are a group of severe congenital malformations, including anencephaly, spina bifida, and encephalocele, which happen when neural tube fails to achieve proper closure during early embryogenesis.Mitochondria are an important site for biological oxidation and substance metabolism, as well as an important component in maintaining homeostasis of the intracellular environment.Mitochondria are also involved in the process of oocyte maturation, fertilization and embryonic development.Normal function of mitochondria is the key to the normal development of embryos.Therefore, mitochondrial dysfunction may be one of the mechanisms of neural tube closure failure.Slc25a32, SHMT2, MTHFD2/MTHFD2L, MTHFD1L and glycine cleavage system(GCS)are a series of key molecules of the mitochondrial one-carbon metabolic pathway.This paper reviews the research progress of mitochondrial dysfunction in the pathogenesis of neural tube malformation by starting from several key molecules and combining with the two main metabolic pathways of one-carbon metabolic chain and oxidative respiratory chain.

Effects of different frequencies of physical training on electron transport chain and oxidative damage in healthy mice

The present study investigated the effect of different frequencies (three and five times a week) on electron transport chain and oxidative stress after 8 weeks of run training. Methods: Eighteen male mice (CF1, 30-35g) were distributed into the following groups (n=6): untrained (UT); trained three-time per week (T3) and trained five- time per week (T5). All training sessions were at the same intensity and duration (45min/day) in a treadmill for small animals. Forty-eight hours after the last training session, the animals were killed by decapitation and quadriceps (red portion) was removed and stored at -70ºC. Succinate dehydrogenase (SDH), complexes I, II, II-III, IV and hydroperoxides were measured. Results: Training sessions for five times per week were more effective in increasing the mitochondrial respiratory chain enzyme activities (SDH, complexes I, II, II-III, IV) as well as in decreasing the formation hydroperoxides than sessions performed for three times training per week (p<0.05). Conclusion: Our findings clearly showed that a higher the frequency of training session promotes a greater activity of the electron transport chain and consequently reduces the oxidative stress in healthy animals.(AU)

Berberine ameliorates lipid accumulation of mouse primary hepatocytes by decreasing fatty acids uptake / 中国药理学通报

Aim To investigate the role of berberine in mouse primary hepatocytes steatosis and whether aden-osine monophosphate-activated protein kinase(AMPK) is essential in this process in order to explore the mech-anism of non-alcoholic fatty liver disease treatment. Methods Different concentrations of oleic acid(OA) were used in mouse primary hepatocytes to determine the appropriate dose inducing steatosis. Subsequently, hepatocytes were treated with berberine and OA at the same time for 24 h serving metformin as positive con-trol. Lactic dehydrogenase (LDH) release test was performed to investigate cell viability. Lipid level was determined by oil red staining and triglyceride assay. Western blot measured the phosphorylation level of AMPK and Acetyl CoA carboxylase. An AMPK inhibi-tor compound C(CC) pre-treated hepatocytes for 1 h followed by berberine 24 h-treatment. The relationship between free fatty acid(FFA) uptake and mitochondri-al inhibition was evaluated by measuring FFA in the supernatant of OA,berberine and rotenone (mitochon-drial complex I inhibitor) group. Results Berberine could significantly reduce primary hepatocytes steatosis induced by oleic acid and stimulate AMPK and ACC phosphorylation at a non-toxic dose. In addition, CC obviously inhibited AMPK activity,but failed to dimin-ish the lipid dysregulation improvement of berberine. Berberine and rotenone intervention reduced OA up-take by 31.2% and 23.6%,respectively. Conclusion Berberine ameliorates hepatocytes lipid accumulation by suppressing fatty acid uptake,which is probably re-sulted from inhibition of mitochondrial respiratory chain complex I,independently of AMPK activation.

Effects of High Intensity Interval Training on the Activity of the Myocardial Mitochondrial Respiratory Chain Complex of Rats / 中国运动医学杂志

Objective To explore the heart function and activity of the mitochondrial respiratory chain complex of rats with myocardial hypertrophy induced by the long-term high-intensity interval training(HIIT).Methods Ninety Wistar rats were randomly divided into an HIIT group,a moderate intensity continuous training(MICT) group and a rest control(RC) group,with each group allocated three subgroups according to the observation time(2,6 and 10 weeks),9 groups altogether(n=10 in each group).Each group was given intervention as their names implied.Then,the heart function was measured using the ultrasoundcardiogram,and the body weight as well as the weight of the heart was weighted.The myocardium mitochondria were extracted using the differential centrifugation after homoge nation to detect the activity of the myocardial and mitochondrial citrate synthase (CS),the activities of the respiratory chain complex C Ⅰ ～CⅣ as well as myocardial protein expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1 α),α-myosin heavy chain (α-MHC),β-MHC,atrial natriuretic factor(ANF) and brain natriuretic peptide(BNP).Results The myocardial hypertrophy was found in HIIT and MICT groups after 1-week and 9-week intervention respectively.At the 2nd and 10th week,no significant differences were found in the heart function,respiratory chain complex activity and protein expression of all three groups(P＞0.05).At the 6th week,the left ventricular ejection fraction,left ventricular fractional shortening,myocardial α-MHC protein expression,and the activities of respiratory chain complex C Ⅰ,C Ⅲ and C Ⅳ of HIIT group were significantly lower while the myocardial β-MHC and BNP protein expression were significantly higher than those of RC and MICT groups(P＜0.05).Conclusion Long-term HIIT but not MICT can induce temporarily pathological myocardial hypertrophy and reduced heart function in Wistar rats,and the mechanism might be related to the downregulation of the myocardial mitochondrial respiratory chain complex activity.

Use of Idebenone for the Treatment of Leber's Hereditary Optic Neuropathy

Abstract Leber's hereditary optic neuropathy (LHON) is one of the most frequent mitochondrial disorders. It is caused by mutations in genes of the mitochondrial DNA coding for subunits of the respiratory chain and leads to severe bilateral vision loss, from which spontaneous recovery is infrequent. Retinal ganglion cells show a selective vulnerability to mitochondrial dysfunction in LHON. Idebenone is the first medication approved for LHON. It is a short-chain benzoquinone, which is an analogue of coenzyme Q10, but with distinct properties and mechanisms of action. Idebenone is a potent antioxidant and inhibitor of lipid peroxidation. Importantly, it facilitates electron flux directly to complex III, bypassing the dysfunctional complex I of the mitochondrial respiratory chain, thereby increasing adenosine triphosphate (ATP) production. In the Rescue of Hereditary Optic Disease Outpatient Study (RHODOS) randomized placebo-controlled clinical trial, 85 patients with LHON were enrolled, in the first 5 years after symptom onset, and randomized to either idebenone 900 mg/d for 6 months or placebo. Idebenone was well tolerated, and although the prespecified primary end point (best recovery in visual acuity [VA]) did not reach statistical significance, all secondary end points (change in best VA, change of VA of best eye at baseline, and change of VA in all eyes) showed a trend toward visual recovery in favor of idebenone. An increasing body of evidence shows that idebenone is effective and safe for the treatment of patients with LHON, including a large retrospective open-label study, several case reports and case series, an expanded access program, and ongoing post-authorization clinical studies. Here, we review the literature on idebenone for the treatment of patients with LHON.

Coenzyme Q10 in the Treatment of Mitochondrial Disease

Abstract Currently, there is a paucity of available treatment strategies for oxidative phosphorylation disorders. Coenzyme Q10 (CoQ10) and related synthetic quinones are the only agents to date that have proven to be beneficial in the treatment of these heterogeneous disorders. The therapeutic efficacy of CoQ10 is not restricted to patients with an underlying CoQ10 deficiency and is thought to result from its ability to restore electron flow in the mitochondrial respiratory chain (MRC) as well as to increase the cellular antioxidant capacity. At present, however, there is no consensus on the appropriate dosage or therapeutic plasma level of CoQ10, and this information will be required before CoQ10 can be utilized effectively in the treatment of mitochondrial disease. The following review will outline our current knowledge on the use of CoQ10 in the treatment of MRC disorders and primary CoQ10 deficiencies.

The role of mitochondrial respiratory chain in hyperbaric oxygen induced reactive oxygen species in HUVEC / 军事医学

Objective To investigate the role of mitochondrial respiratory chain (MRC) in induction of reactive oxygen species (ROS) by hyperbaric oxygen (HBO).Methods Superoxide anion (O·-2) specific fluorescence probe DHE and mitochondrial O·-2 probe Mito-SOX were used to label ROS in human umbilical vein endothelium cells(HUVEC) microscopically after HBO exposure.Results After HBO exposure, O·-2 increased (31±8)% and (137±19) % in whole cells and in mitochondria, respectively (P<0.01).These increments were suppressed by MRC complex Ⅱ inhibitor TTFA for (55±11)% in whole cells (P<0.05)and (61±8) % in mitochondria(P<0.01).Conclusion MRC may be the main source of ROS induced by HBO in HUVECs.

TNF-α induced RIP1-dependent apoptosis in L929-A cells by interrupting mitochondrial respiratory chain complex Ⅲ / 军事医学

Objective To explore the mechanism by which tumor necrosis factor alpha(TNF-α) induces RIP1 kinase-dependented apoptosis in L929-A fibroblastoma cells.Methods The sub-mitochondrial localization of receptor-interacting protein 1(RIP1),caspase-8 and Bid proteins was detected by dose-gradient trypsin digestion and Western blotting.The levels of reactive oxygen species (ROS),intracellular calcium concentration,mitochondrial membrane potential (MMP),and cellular adenosine triphosphate(ATP) content were determined by fluorescent probe labeling and flow cytometry assay.The mitochondrial respiratory chain complex Ⅰ and Ⅲ activities were detected by commercial kits.Nec-1,A RIP1 kinase specific inhibitor,and RIP1-/-or Bid-/-L929-A cells were used to detect the roles of RIP1 kinase and Bid protein in cell death.Results RIP1,caspase-8 and Bid proteins were co-located in the outer membrane of mitochondrial.TNF-α exposure for 3 h could induce Bid cleavage,inhibit mitochondrial respiratory chain complex Ⅲ activity and reduce MMP.Following these changes and after TNF-α exposure for 6-12 h,the intracellular calcium concentration and ROS were increased,whereas the ATP concentration was decreased,and the cells were killed.Inhibiting RIP1 kinase or knockdown RIP1 or Bid protein could suppress all the cytotoxic effects of TNF-α.Conclusion TNF-α treatment can result in RIP1 kinase-mediated Bid cleavage and inhibit mitochondrial respiratory chains and cell energy metabolism,which ultimately leads to the death of L929-A cells.

Effect of a Decoction to Nourish Qi and Invigorate the Spleen on the Activity of Mitochondrial Respiratory Chain Enzyme Complexes in Cardiomyocytes of Rats with Spleen Qi Deficiency Syndrome / 中国医科大学学报

Objective To investigate the effect of a decoction to nourish qi and invigorate the spleen on mitochondrial respiratory chain enzyme complex activity in cardiomyocytes of rats with spleen qi deficiency syndrome. Methods Rats were randomly divided into normal,model,and treatment groups. The model and treatment groups were treated by diet intervention combined with the limit swim method. The general condition and spleen qi deficiency syndrome were assessed on day 15. After the success of the model,the normal and model groups were treated with a con?ventional feeding method combined with normal saline ,and the treatment group was treated by diet intervention combined with a decoction to nour?ish qi and invigorate the spleen for 9 weeks. The activity of two mitochondrial respiratory chain enzyme complexes was observed. Results The ac?tivity of mitochondrial respiratory chain enzyme complexⅡand complexⅣin the model group was significantly lower than the activity in the nor?mal and treatment groups(P<0.05). The activity levels of complexⅡand complexⅣwere significantly different between the model group and the treatment group(P<0.05). Conclusion Spleen qi deficiency can cause decreased activity of mitochondrial respiratory chain enzyme com?plexes in myocardial cells. The decoction to nourish qi and invigorate the spleen can modulate the activity of myocardial mitochondrial respiratory chain enzyme complexesⅡandⅣ.

The mitochondrial toxicity of bentysrepinine on HepG2 cells / 中国药理学通报

Aim To provide references for clinical trials dose and rational drug use by evaluating mitochondrial toxicity of bentysrepinine on HepG2 cells.Methods Mitochondrial toxicity of bentysrepinine on HepG2 cells was cmomprehensively evaluated by measuring proliferation inhibition rate, lactic acid content in culture supernatant, reactive oxygen species(ROS) content, mitochondrial membrane potential (MMP) variation and the activity of mitochondrial respiratory chain complex enzymes Ⅰ to Ⅳ.Results The half inhibitory concentration of bentysrepinine of HepG2 cells was 359 μmol·L-1.Compared with the control group, bentysrepinine could reduce the MMP, raise the level of lactic acid, increase the content of ROS and lower the activity of mitochondrial respiratory chain complex enzymes Ⅰ to Ⅲ with the concentration of 400 μmol·L-1(196 mg·L-1), showing an obvious mitochondrial toxicity.Compared with lamivudine and adefovir dipivoxil, bentysrepinine exerted no influence on indexes above with the same concentration 100 μmol·L-1.Conclusions Bentysrepinine shows an obvious mitochondrial toxicity on HepG2 cells with the concentration of 400 μmol·L-1.This mitochondrial toxicity is not presented with the concentration of 200 μmol·L-1.It shows that the safety range of bentysrepinine about mitochondrial toxicity is relatively wide.The test plays a guiding role in clinical trial dose design as well as clinical treatment.

Ultrastructural Changes in Skeletal Muscle of Infants with Mitochondrial Respiratory Chain Complex I Defects

BACKGROUND AND PURPOSE: The pathogenesis of mitochondrial disease (MD) involves the disruption of cellular energy metabolism, which results from defects in the mitochondrial respiratory chain complex (MRC). We investigated whether infants with MRC I defects showed ultrastructural changes in skeletal muscle. METHODS: Twelve infants were enrolled in this study. They were initially evaluated for unexplained neurodegenerative symptoms, myopathies, or other progressive multiorgan involvement, and underwent muscle biopsies when MD was suspected. Muscle tissue samples were subjected to biochemical enzyme assays and observation by transmission electron microscopy. We compared and analyzed the ultrastructure of skeletal muscle tissues obtained from patients with and without MRC I defects. RESULTS: Biochemical enzyme assays confirmed the presence of MRC I defects in 7 of the 12 patients. Larger mitochondria, lipid droplets, and fused structures between the outer mitochondrial membrane and lipid droplets were observed in the skeletal muscles of patients with MRC I defects. CONCLUSIONS: Mitochondrial functional defects in MRC I disrupt certain activities related to adenosine triphosphate synthesis that produce changes in the skeletal muscle. The ultrastructural changes observed in the infants in this study might serve as unique markers for the detection of MD.

Coenzyme Q10 defects may be associated with a deficiency of Q10-independent mitochondrial respiratory chain complexes

BACKGROUND: Coenzyme Q10 (CoQ10 or ubiquinone) deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC) spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III) while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %), thus confirming CoQ10 disease. CONCLUSIONS: Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.

Zhibai Dihuang Decoction improves the activity of sperm mitochondrial respiratory chain complex in rats with Ureaplasma urealyticum infection / 中华男科学杂志

<p><b>Objective</b>To investigate the effect of Zhibai Dihuang Decoction (ZDD) on the sperm mitochondrial respiratory chain complex (MRCC) in rats with Ureaplasma urealyticum (UU) infection.</p><p><b>METHODS</b>Ninety male SD rats were randomly divided into five groups, sham operation, UU infection model control, ZDD (crude drug at 8.56 g per kg of the body weight per day), doxycycline (DC, at 20 mg per kg of the body weight per day), and ZDD+DC. The model of UU infection was established by injecting UU into the bladder of all the rats except those of the sham operation group. After modeling, the rats were treated intragastrically with respective drugs for 21 days and then executed and their epididymides harvested for examination of sperm quality and determination of the activities of sperm MRCCs I, II, III and IV by spectrophotometry.</p><p><b>RESULTS</b>At 10 days after modeling, the UU-positive rates in the model control, sham operation, ZDD, DC and ZDD+DC groups were 92.9%, 0%, 33.3%, 26.7% and 20.0%, respectively, significantly higher in the model control than in the other groups (P<0.05). The epididymal sperm concentrations in the five groups were (0.97±0.23), (3.02±0.52), (1.21±0.35), (1.02±0.31) and (1.52±0.28) ×106 ml, the sperm motilities were (58.62±15.36), (80.45±7.21), (75.52±8.78), (68.43±10.25) and (78.25±7.67)%, and rates of grade a+b sperm were (6.15±1.02), (10.32±1.14), (10.12±1.08), (9.01+1.27) and (10.74±1.03)%, respectively, all remarkably lower in the model control than in the sham operation group (P<0.01), but markedly higher in the ZDD and ZDD+DC groups than in the model controls (P<0.05). The activities of MRCC I in the model control, sham operation, ZDD, DC and ZDD+DC groups were (31.54±16.25), (136.86±6.34), (100.68±14.41), (81.68±6.78) and (124.06±5.54) μmol/(min·mg), those of MRCC II were (9.50±3.86), (20.34±0.37), (10.88±1.04), (12.93±1.07) and (16.23±0.60) μmol/(min·mg), those of MRCC III were (5.58±1.79), (19.60±0.61), (11.34±1.35), (13.87±1.23) and (15.96±0.69) μmol/(min·mg), and those of MRCC IV were (9.54±1.34), (28.98±3.33), (17.02±2.04), (18.41±2.67) and (21.66±2.93) μmol/(min·mg), respectively, all significantly lower in the model control than in the sham operation group (P<0.01), with the activities of MRCCs I, III and IV remarkably higher in the ZDD, DC and ZDD+DC groups (P<0.01) and that of MRCC II higher in the DC and ZDD+DC groups than in the model control (P<0.05).</p><p><b>CONCLUSIONS</b>ZDD can improve the epididymal sperm quality and the activity of the sperm MRCC in UU-infected rats, which may be one of the mechanisms of ZDD acting on male infertility caused by UU infection.</p>

Progress of mitochondrial respiratory chain dysfunction in septic children / 国际儿科学杂志

Sepsis is a complicated pathophysiological disorder arising from a systemic inflammatory response to infection.Because of high morbidity,high mortality and high cost of treatment, sepsis has caused global attention and become a hot spot in pediatric intensive medical research.Increasing number of studies have shown a close correlation between the occurrence of multiple organ dysfunction syndrome and mitochondrial dysfunction in sepsis.A major feature in sepsis is dysfunction of mitochondrial oxidative phosphorylation.This review discusses the dysfunction of mitochondrial respiratory chain in sepsis.

Effect of inhibiting mitochondrial respiratory chain complex I on migration and invasion capacity of colon cancer cell line Caco2 / 第二军医大学学报

Objective To investigate the effect of inhibiting mitochondrial respiratory chain complex I on the migration and invasion capacity of colon cancer cell line Caco2, and to explore the possible molecular mechanism. Methods Human colon cancer cell line Caco2 was treated with 1 μmol/L rotenone in vitro. Then the relative activity of mitochondrial respiratory chain complex I was examined by chromatometry, the capacity of cell migration and invasion was determined by trans well assay, and the reactive oxygen species (ROS) level in cells was determined using flow cytometry. Results The activity of mitochondrial respiratory chain complex I of Caco2 cells treated with 1 μmol/L rotenone was significantly lower than that of the untreated cells(P<0. 01). In addition, Transwell assay showed that the cell migration rate and invasive rate in Caco2 cells treated with rotenone were significantly higher than those in untreated Caco2 cells after 48 h (migrant rate [30. 4±1. 4]% vs [22. 6 ± 1. 4]%, invasive rate [20. 3 ± 1. 0]% vs [15. 2 ± 1. 3] %, P<0. 01). Furthermore, the ROS level in the rotenone treated cells was significantly higher than that in untreated cells ([5. 68 ± 0. 44] Y vs [3. 46 ± 0. 30]%, P<0. 01). Conclusion Our data suggest that inhibiting the activity of mitochondrial respiratory chain complex I may promote cell migration and invasion by increasing ROS production in colon cancer cells.

Mitochondrial function and its correlation with age in articular chondrocytes of Kashin-Beck disease / 西安交通大学学报(医学版)

Objective To evaluate the mitochondrial function of chondrocytes in Kashin-Beck disease (KBD) patients and its correlation with age.Methods Mitochondrial function was evaluated by analyzing the activities of respiratory chain enzyme complexes and citrate synthase (CS),intracellular adenosine triphosphate (ATP)contents, changes in mitochondrial membrane potential (ΔΨm),as well as the intracellular reactive oxygen species (ROS) contents.Correlation of mitodhondrial function and age was analyzed with linear regression.Results Activities of complexes Ⅱ (P = 0.001 ),Ⅲ (P = 0.005 )and Ⅳ (P = 0.005 )were reduced in KBD articular chondrocytes compared with cells from normal controls.However,the mitochondrial mass was increased in KBD samples. Cultured KBD chondrocytes had reduced cellular ATP level (P = 0.001 )and mitochondrial membrane potential (P =0.001),but increased citrate synthase activity (P =0.04)and intracellular ROS level (P <0.001).We found no correlation between mitochondrial function and donor age either in normal or in KBD chondrocytes. Conclusion Mitochondrial function is altered in articular chondrocytes of KBD,and no correlation was found between mitochondrial function and donor age.

Fluvoxamine alters the activity of energy metabolism enzymes in the brain

Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent. .

New mathematical derivations for calculation of ATP yield due to the complete oxidation of different types of fatty acids.

During the complete oxidation of fatty acids, the electrons removed from fatty acids in different forms (FADH2 and NADH2) pass through the respiratory chain, driving the ATP synthesis. Generally, the ATP yield due to the complete oxidation of fatty acids is calculated by sum total the ATPs obtained due to the oxidation of FADH2 and NADH2 due to lack of any particular method. This calculation is simple for saturated even numbered fatty acids, but in the case of saturated and unsaturated odd numbered fatty acids the calculation of ATP yield is difficult and needs mathematical calculations due to some changes in their β-oxidation pathway when compared to the pathway of saturated even numbered fatty acids. These calculations are made simple by our derivations and following formulae where we require only number of carbon atoms and double bonds present in a fatty acid. Our method is superior and easier in comparison to long mathematical calculations that are in the practice.

Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain

Objective: To investigate the effects of cannabidiol (CBD) on mitochondrial complex and creatine kinase (CK) activity in the rat brain using spectrophotometry. Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg) in an acute (single dose) or chronic (once daily for 14 consecutive days) regimen. The activities of mitochondrial complexes and CK were measured in the hippocampus, striatum, and prefrontal cortex. Results: Both acute and chronic injection of CBD increased the activity of the mitochondrial complexes (I, II, II-III, and IV) and CK in the rat brain. Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology of mood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex and CK activity) by CBD could be an important mechanism implicated in the action of CBD. .