Caffeine Treatments Research Articles

Metformin and Caffeine’s Influence on Lipid Profile Indices of Streptozotocin-Induced Dyslipidemia in an Animal Model

Dyslipidemia has been linked to insulin resistance and hyperglycemia. Hyperglycemia, which is the outcome of either insufficient insulin production or insensitivity to insulin, is the hallmark of diabetes mellitus (DM). In this study, thirty-six (36) male Wistar rats with diabetes induced by streptozotocin were used to determine the effect of metformin and caffeine on blood glucose levels and lipid profile indices. The rats weighed between 150 and 200 grams and were split into six groups of six animals each at random. Group A was given unlimited access to chow (Grower feed) and water adlibitum. Group B was administered 60 mg/kg of streptozocin (STZ) without any medication, while Group C was given 60 mg/kg of STZ together with 50 mg/kg of metformin. Groups D and E were administered 60 mg/kg of streptozocin and 25 mg/kg and 50 mg/kg of caffeine, for a duration of 21 days respectively. Group F was given 50 mg/kg of caffeine together with 50 mg/kg of metformin for a duration of 21 days. After performing a post-hoc LSD comparison and using ANOVA to analyze the results, the lipid profile and blood glucose level were deemed significant at p<0.05. A paired t-test was used to analyze body weight. Rats with diabetes had reduced body weight, whereas those receiving metformin and caffeine treatments had noticeably increased body weight. The findings demonstrated that whereas metformin and caffeine therapy greatly reduced blood glucose levels, STZ caused hyperglycemia in group B. However, diabetic rats had considerably higher levels of triglycerides (TG) and total cholesterol (TC), which were reduced by metformin and caffeine administration. HDL activity was considerably increased after treatment with metformin and caffeine, despite the rats' reduced HDL levels in group B. Rats with diabetes had considerably elevated levels of LDL and VLDL, and therapy with metformin and caffeine markedly restored their activity. The study shows that caffeine plus metformin may be utilized to control the lipid profile and blood glucose levels in diabetic rats.

Impacts of caffeine on fathead minnow behaviour and physiology

Pollution from regularly used substances such as pharmaceuticals, cleaning agents, and even food and beverages is an increasing problem in the environment. Caffeine, a commonly ingested stimulant, is one such contaminant that has been detected in aquatic environments worldwide. Yet, little is known about how ecologically relevant concentrations of caffeine influence the morphology, behaviour, and physiology of exposed organisms. To address this knowledge gap, we exposed fathead minnow (Pimephales promelas) to three caffeine treatments: a freshwater control (nominal: 0 ng/L), a low (nominal: 1,000 ng/L) and high environmentally relevant dose (nominal: 10,000 ng/L), for 35 days. We tested the learning abilities, anxiety, metabolic rates, and morphological features of exposed vs. control fish. Caffeine exposure did not affect the ability of fish to learn but did influence anxiety levels. Over the course of repeated anxiety testing, unexposed control fish visited a black square more often while fish exposed to low levels of caffeine did not, potentially indicating that these fish remained in a more anxious state. While caffeine did not impact metabolism, fish growth, or body size, it was associated with lower liver investment—although this response was only observed in our low caffeine treatment. Overall, our results suggest that even relatively low concentrations of caffeine may impact the liver size and anxiety of exposed fish, but further research is needed to assess how extended exposure to caffeine impacts fitness. Given the increase in anthropogenic contaminants in aquatic environments, it is important that we continue to investigate their effects on the organisms exposed to them.

The use of mud in cellulite reduction. Case report

Mud is a natural, organic and mineral raw material used in the cosmetic industry, rehabilitation and wellness. In cosmetology, it is mainly used in the prevention of cellulite and stretch marks, and in skin care. This study aimed to evaluate the effect of mud and caffeine treatments on cellulite reduction. A 49-year-old woman with confirmed cellulite on the back of her thighs underwent a series of ten mud treatments. The first effects were observed after just five treatments. The results of the study confirm that the mud, in combination with caffeine, has a beneficial effect on reducing visible bumps on the skin. The disadvantage of the treatment may be the unpleasant smell.

Assessing Caffeine's Neuroprotective Effects on Rotenone-Induced Parkinson's Disease: Unravelling the Neurological Dynamics of Striatal Impact

The alarming prevalence of Parkinson's disease (PD) has prompted a search for standard therapeutic interventions capable of altering or halting its progression. Identifying a neuroprotective or disease-modifying therapy for PD is akin to pursuing the Holy Grail. Numerous studies have affirmed the therapeutic benefits of adenosine A2A receptor blockade in alleviating both motor and non-motor symptoms in PD. Furthermore, A2A receptors are selectively localized in the basal ganglia. This study aimed to evaluate the impact of caffeine on the striatum of rats with PD induced by rotenone. Fifty adult male Wistar rats, weighing between 150 and 200g, were utilised in this study. The rats were randomly assigned to five groups, each consisting of ten rats: Group A (vehicle group, alcohol, 3mL/kg), group B (rotenone-only treated with 3mg/kg, ip.), group C (caffeine 30mg/kg + rotenone 3mg/kg, ip.), group D (rotenone 3mg/kg + caffeine 30mg/kg, ip.), and group E (caffeine-only treated with 30mg/kg, ip.). The findings revealed a significant (p<0.05) reduction in body weight and relative brain weight in response to caffeine treatments. Rotenone administration induced histological changes akin to those observed in PD, encompassing neuronal structural derangement, degenerated striatal bundled fibre, and loss of myelinated neurons and Nissl substance. This study adds to the growing body of research supporting the therapeutic potential of caffeine in PD. The results highlight caffeine's neuroprotective properties and its ability to mitigate striatal lesions. The pursuit of effective interventions for PD remains crucial, and caffeine emerges as a promising therapeutic agent in this regard.

Exploring toxicological interactions in a changing sea: The case of the alkaloids caffeine and caulerpin

The bisindolic alkaloid caulerpin (CAU) is a bioactive compound isolated from green algae of the genus Caulerpa that are highly invasive in the Mediterranean Sea. On the other side, the purine alkaloid caffeine (CAF) is one of the most globally consumed psychoactive substances and a widespread anthropogenic water pollutant. Both compounds display a large panel of biological properties and are well known to accumulate in the tissues of aquatic organisms and, in certain circumstances, co-occur in the human diet. On this premise, the present study aimed to investigate possible synergistic interactions between CAU and CAF by using the bivalve Mytilus galloprovincialis as a model organism. Mussels were exposed to CAF via medium while they were fed with food enriched with CAU. After treatments, biochemical analysis confirmed the toxic potential of CAF, with increased AChE activity and lipid peroxidation. Also, histopathological alterations were observed in the gills and digestive tubules. The NMR-based metabolomics analysis detected higher levels of free amino acids under CAF treatments. Conversely, the food administration of CAU did not affect the above toxicological biomarkers. In addition, we did not observe any cumulative effect between CAF and CAU toward increased cellular damage and neurotoxicity. On the other hand, a possible action of CAU in decreasing CAF toxicity could be hypothesized based on our results. This hypothesis is supported by the activity of CAU as an agonist of peroxisome proliferator-activated receptors (PPARs). PPARs mediate xenobiotic detoxification via cytochromes P450, which is involved in CAF metabolism. Overall, the results obtained not only rule out any cumulative adverse effects of CAF and CAU but also encourage further research to evaluate the possible use of CAU, a compound easily obtained through the valorization of biomass from invasive species, as a food additive to improve the clearance of xenobiotics.

Caffeine alleviates anxiety-like behavior and brainstem lesions in a rotenone-induced rat model of Parkinson's disease

BackgroundParkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms. In 2016, approximately 6.1 million individuals were affected by PD, with 211,296 deaths attributed to the disease. The understanding of PD initially came from the observation of dopaminergic system alterations in a specific region of the brainstem, indicating that the core motor and non-motor features of PD are closely associated with brainstem dysfunction. The primary treatment approach for PD revolves around dopamine replacement, as many of the symptoms are responsive to this therapeutic intervention. However, long-term administration of this approach is linked to several complications, and a definitive gold-standard therapy for PD is yet to be identified. The pharmacological management of PD has been challenging and inconsistent, mainly due to the unclear underlying cause of the disease. This study aims to evaluate the effects of caffeine on the brainstem of rats with PD induced by rotenone. MethodologyFifty adult male Wistar rats weighing between 150 and 200 g were used in this study. The rats were randomly divided into five groups of ten rats each: Vehicle Group, Rotenone-only treated Group (rotenone only treated with 3 mg/kg, intraperitoneal administration [IP]), Preventive Group (caffeine 30 mg/kg + rotenone 3 mg/kg, IP), Curative Group (rotenone 3 mg/kg + caffeine 30 mg/kg, IP), and Caffeine only treated Group (caffeine only treated with 30 mg/kg, IP). The animals underwent neurobehavioral assessments, followed by sacrifice. The brains were then excised, weighed, and processed histologically. Appropriate brain sections were taken and processed. Photomicrographs were obtained, morphometric and statistical analysis was performed using an Omax LED digital ResultsThe results demonstrated a significant (p < 0.05) reduction in body weight and relative brain weight, which were increased by caffeine treatments. Rotenone administration led to histological changes similar to those observed in PD, including neuronal structural derangement, degenerated nerve fibers, loss of myelinated neurons, and Nissl substance, as well as downregulation in the expressions of NRF2 and TH in the midbrain. However, these pathological features were counteracted or ameliorated by caffeine treatment. ConclusionOur study contributes additional evidence to the growing body of research supporting the therapeutic potential of caffeine in Parkinson's disease (PD). The results underscore the neuroprotective properties of caffeine and its capacity to mitigate oxidative stress by modulating TH (tyrosine hydroxylase) and cytoplasmic NRF2 (nuclear factor erythroid 2-related factor 2) in the mesencephalon. These findings suggest that caffeine holds promise as a viable treatment option for PD.

Effects of epigallocatechin gallate, caffeine, and their combination on fat accumulation in high-glucose diet-fed Caenorhabditis elegans.

Epigallocatechin gallate (EGCG) and caffeine are inevitable to be ingested together in the process of drinking green tea. This study used Caenorhabditis elegans as an organism model to examine whether the binding of EGCG and caffeine could influence the fat-reduction effect. The results revealed that EGCG significantly reduced the Nile Red fluorescence intensity and the triglyceride/protein ratio of the C. elegans obesity model by 14.7% and 16.5%, respectively, while the effect of caffeine was not significant. Moreover, the degree of reduction in fluorescence intensity and triglyceride/protein ratio by EGCG+caffeine was comparable to that of EGCG. In the exploration of underlying mechanism, we found that EGCG and EGCG+caffeine treatments had no influence on food intake and energy expenditure of C. elegans. Their fat-reduction effects were dependent on the regulation of lipogenesis, as shown by the decreased expression of the sbp-1, fat-7, and daf-16 genes.

Chlorophyll Content and Leaf Morphological Features of Capsicum annum L. cv. ‘Alexander’ under Yeast and Caffeine Tested as Bio-fertilizers

Bio-fertilizers are in the present more and more of interest as alternative nutritive inputs. This research aim was to test different doses of yeast and caffeine on pepper growth and chlorophyll content. The experiment in controlled conditions consisted of 8 phytocosms treatments with 3 yeast and caffeine doses 1%, 2%, and 3%, one mixed treatment (2%), and the control treatment in five replications. The yeast addition promoted all the tested morphological parameters especially the middle dose tested. Caffeine treatments induced a slow growth of pepper vegetative period, even a delayed development compared with the control treatment. In conclusion, the mixed treatment was the most efficient pepper bio-fertilizer and provided the highest values of leaf length, width, seedling height, and also total chlorophyll content.

Istradefylline modulates purinergic enzymes and reduces malignancy-associated factors in B16F10 melanoma cells.

ATP and adenosine exert pivotal roles in the development, maintenance, and metastatic spreading of melanoma. The action of such key melanoma tumor microenvironment (TME) constituents might be complementary or opposed, and their effects are not exclusive to immune cells but also to other host cells and tumor cells. The effects of ATP are controlled by the axis CD39/73, resulting in adenosine, the main actor in the TME, and A2A is the crucial mediator of its effects. We evaluated ATP and adenosine signaling through A2A on B16F10 melanoma cells using istradefylline (IST) (antiparkinsonian A2A antagonist) and caffeine (CAF) treatments after exposure to ATP and adenosine. Adenosine increased melanoma cell viability and proliferation in a concentration-dependent manner. ATP increases viability only as a substrate by CD39 to produce adenosine. Both IST and CAF are toxic to B16F10 cells, but only IST potentialized paclitaxel-induced cytotoxic effects, even decreasing its IC50 value. IST positively modulated CD39 and CD73 expression. CD39 activity was increased, and E-ADA was reduced, indicating that the melanoma cells promoted compensatory feedback in the production and maintenance of adenosine levels. A2A antagonism by IST reduced the factors associated with malignancy, like migration, adhesion, colony formation, and the capacity to produce melanin. Moreover, IST significantly increases nitric oxide (NO) production, which correlates to a decline in melanoma cell viability by apoptotic events. Altogether, our results suggest that adenosine signaling through A2A is essential for B16F10 cells, and its inhibition by IST causes compensatory purinergic enzymatic modulations. Furthermore, IST is a promising therapy that provides new ways to improve current melanoma treatments.

The Antifungal and Antibiofilm Activities of Caffeine against Candida albicans on Polymethyl Methacrylate Denture Base Material.

Background: In this study, the effect of pure caffeine was established against Candida albicans (C. albicans) using different microbiological techniques. Methods: Broth microdilution and colony forming units (CFUs) assays were used to detect the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). The Live/Dead fluorescent dyes were implemented to determine the yeast viability. Polymethyl methacrylate acrylic resin (PMMA) discs were prepared to evaluate caffeine’s effects against adherent C. albicans using microplate reader, CFUs, and scanning electron microscope (SEM). Results: caffeine’s MIC was detected around 30 mg/mL, while the MFC was considered at 60 mg/mL. In an agar-well diffusion test, the inhibition zones were wider in caffeine groups. The Live/Dead viability test verified caffeine’s antifungal effects. The optical density of the adherent C. albicans on PMMA discs were lower at 620 nm or 410 nm in caffeine groups. CFU count was also reduced by caffeine treatments. SEM revealed the lower adherent C. albicans count in caffeine groups. The effect of caffeine was dose-dependent at which the 60 mg/mL dose demonstrated the most prominent effect. Conclusion: The study reinforced caffeine’s antifungal and antibiofilm properties and suggested it as an additive, or even an alternative, disinfectant solution for fungal biofilms on denture surfaces.

Effective Home Remedies that Provide Quick Relief for Puffy Eyes

Background: Periorbital edema is a major cosmetic concern for women across all the ages. Many lifestyle changes contribute to the worsening of puffy eyes in all age groups, while aging, chronic medical conditions are also a factor. The purpose of this study is to identify the various remedies women use to treat periorbital edema with a focus on studying homemade remedies, their mechanism of action and their effectivity. Study around this topic is important as there is a distinct lack of literature on a topic that is a cosmetic concern for women. Method: An online survey of 14 questions was conducted asking questions regarding periorbital edema and the quick effective homemade remedy used by them. Results: 50.8% (n=61) participants deal with puffy eyes while 49.2% (n=59) did not. From the 61 participants who dealt with eye puffiness, only 37.7% (n=23) took active measures to counteract it. From 23 respondents, it was found that most found using cold compression (n=17), getting enough sleep (n=11), and cucumbers (n=11) the most effective in dealing with eye puffiness, while vitamin E, K, caffeine treatments and witch hazel were less popular. Majority found these methods effective ‘sometimes’, and only one person didn’t find them effective. Conclusion: Women find cold compression, cucumber, and getting enough sleep most effective. Although more than half the participants of the survey dealt with eye puffiness, majority chose not to treat them.

Anti-inflammatory activity of caffeine (1,3,7-trimethylxanthine) after experimental challenge with virulent Listeria monocytogenes in Swiss mice

BackgroundImmunomodulatory therapies are claimed to enhance antimicrobial immunity and counterbalance antimicrobial resistance mechanisms of pathogenic bacteria. PurposeTo investigate whether caffeine can be useful for control of inflammation derived from experimental systemic infection with Listeria monocytogenes. MethodsPeritoneal macrophages (pMØ) from Swiss mice were cultured with caffeine in 96-well plates, and then infected with virulent L. monocytogenes 619. In another experiment, the pMØ were first infected with the bacterium and then treated with caffeine. Swiss mice were inoculated intraperitoneally with L. monocytogenes and then treated intravenously with caffeine (0.05; 0.5 or 5 mg/Kg). ResultsCaffeine did not exert direct antibacterial activity in vitro against L. monocytogenes. Macrophages exposed to caffeine before or after infection with L. monocytogenes had increased cell viability, although the intracellular bacterial loads were similar to the control groups. Caffeine treatments of Swiss mice reduced leukocyte infiltration into the peritoneal cavity after L. monocytogenes infection. However, the bacterial burden was reduced in the spleen and liver. The mRNA expressions of IL-1β, IL-6 and the enzyme inducible nitric oxide synthase (iNOS) were reduced whereas IL-10 was increased. ConclusionCaffeine has an anti-infectious potential and ameliorated infection-derived inflammation following experimental infection with L. monocytogenes.

Influence of selected storage temperatures on wood properties and its biological resistance after the use of methylxanthines

Methylxanthine’s fungicidal properties were investigated, with attention to the temperature of treatment. Caffeine and theophylline treatments of beech and spruce woods were applied for three months in the temperature range of -20 to 40 °C, simulating potential weather conditions in the European region and temperatures specific for various wood applications (cellars, wine cellars, room indoor temperatures, interior trusses). Effects of the selected temperatures were considered without the influence of the other possible factors, which have been considered in previous studies (e.g. effects of temperature in combination with other factors such as UV radiation, humidity, and chemical or biological degradation). Then, the specimens were exposed to a mix of molds and fungi for three months under controlled laboratory conditions in order to analyze a possible subsequent biological attack. The results did not show any effect of temperature of the methylxanthine treatment within the studied range on the organismal activity. Caffeine exhibited a better protective potential than theophylline and was more effective for spruce than for beech. The results indicated the suitability of caffeine for protection of spruce and spruce-based materials in interior applications at a stable temperature without significant effects of UV and humidity.

Maternal caffeine administration to ewes does not affect perinatal lamb survival

Perinatal mortality of lambs is the major source of reproductive loss in extensive sheep production systems. Treatment with caffeine has reduced intra-partum mortality and/or improved metabolic indicators in other species following hypoxia. This study was conducted to evaluate the efficacy of caffeine for improving perinatal lamb survival. Experiment 1 comprised group-fed Merino ewes grazing pasture and offered 1.8 g/day (estimated 20 mg/kg live weight) caffeine throughout a 4-week lambing period, and a control without caffeine. The survival of lambs to marking (vaccinated, tail docked, males castrated) age in the caffeine treatment group (0.81) did not differ (P = 0.199) from that of control lambs (0.73; total born n = 877). Experiment 2 comprised Merino ewes lambing from three successive weekly joining groups. Treated ewes were drenched with an aqueous caffeine solution at a dose rate of 10 mg/kg live weight from the day before anticipated lambing, until the individual lambed. Control ewes were drenched with water. The proportion of lambs born dead (0.07) and the survival of lambs to marking age (caffeine 0.61; control 0.62) were similar between treatment groups (total born n = 1158). In both experiments, ewe mortality and the weight of lambs at marking were not altered by caffeine treatments. The results from this large-scale field study indicate caffeine is not an effective therapeutic agent to increase either intra-partum or perinatal survival, or lamb growth rates.

Effects of temperature on caffeine and carbon nanotubes co-exposure in Ruditapes philippinarum

In the marine environment, organisms are exposed to a high and increasing number of different contaminants that can interact among them. In addition, abiotic factors can change the dynamics between contaminants and organisms, thus increasing or even decreasing the toxic effect of a particular compound. In this study, the effects of caffeine (CAF) and functionalized multi-walled carbon nanotubes (f-MWCNTs) induced in the clam Ruditapes philippinarum were evaluated, acting alone and in combination (MIX), under two temperature levels (18 and 21 °C). To assess the impact of such compounds, their interaction and the possible influence of temperature, biochemical and histopathological markers were investigated. The effects of f-MWCNTs and caffeine appear to be clearly negative at the control temperature, with lower protein content in contaminated clams and a significant decrease in their metabolism when both pollutants were acting in combination. Also, at control temperature, clams exposed to pollutants showed increased antioxidant capacity, especially when caffeine was acting alone, although cellular damages were still observed at CAF and f-MWCNTs treatments. Increased biotransformation capacity at 18 °C and MIX treatment may explain lower caffeine concentration observed. At increased temperature differences among treatments were not so evident as at 18 °C, with a similar biological pattern among contaminated and control clams. Higher caffeine accumulation at MIX treatment under warming conditions may result from clams’ inefficient biotransformation capacity when exposed to increased temperatures.

Green coffee extract attenuates Parkinson's-related behaviors in animal models.

Epidemiological studies have shown an inverse association between coffee consumption and the development of Parkinson's disease (PD). The effects of the oral treatment with green (non-roasted) coffee extracts (CE, 100 or 400 mg/kg) and caffeine (31.2 mg/kg) were evaluated on catalepsy induced by haloperidol in mice, and unilateral 6-OHDA lesion of medial forebrain bundle (MFB) or striatum in rats. Also, the in vitro antioxidant activity and the monoamine levels in the striatum were investigated. CE presented a mild antioxidant activity in vitro and its administration decreased the catalepsy index. CE at the dose of 400 mg/kg induced ipsilateral rotations 14 days after lesion; however, chronic 30-day CE and caffeine treatments did not interfere with the animals' rotation after apomorphine or methamphetamine challenges in animals with MFB lesion, nor on monoamines levels. Furthermore, CE and caffeine were effective in inhibiting the asymmetry between ipsilateral and contralateral rotations induced by methamphetamine and apomorphine in animals with lesion in the striatum but did not avoid the monoamines depletion. These results indicate that CE components indirectly modulate dopaminergic transmission, suggesting a pro-dopaminergic action of CE, and further investigation must be conducted to elucidate the mechanisms of action and the possible neuroprotective role in PD.

Caffeic acid and caffeine attenuate toxicity associated with malonic or methylmalonic acid exposure in Drosophila melanogaster.

The deficiency in the activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MCM, EC 5.4.99.2) leads to a condition called methylmalonic academia, which is characterised by the accumulation of methylmalonic (MMA), malonic (MA) or other organic acids. Importantly, we have recently found that supplementation with Ilex paraguariensis aqueous extract offered protection against toxicity associated with MMA or MA exposure to Drosophila melanogaster. Of note, caffeic acid (CA) and caffeine (CAF) were the major phytochemicals found in our Ilex paraguariensis crude extract. Therefore, here, we have exploited CA and/or CAF to test the hypothesis that supplementation with the isolated compounds (either alone or combined) could exert a protective effect against MMA or MA-induced toxicity in flies. Therefore, flies were exposed to MA (5mM) or MMA (5mM) and concomitantly treated with CA (1.39μg/mL), CAF (1.27μg/mL) or CA + CAF for 10days for survival, and for 4days for behavioural and biochemical assays. CA, CAF and CA + CAF treatments completely abolished the mortality associated with either MMA or MA exposure. Moreover, CA and CAF, either alone or combined, completely abolished behavioural changes, and completely protect against changes in thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT) activity and MTT reduction ability, associated with MA or MMA exposure. In turn, CAF restored SOD activity in the head of flies exposed to MA or MMA. However, CA and CAF (either alone or combined) significantly decreased acetylcholinesterase (AChE) activity per se, while CAF alone protected from changes in AChE activity (in head tissue) associated with MA or MMA. Finally, CA and/or CAF were able to protect from a decrease in glucose and triglyceride levels associated with both MA and MMA exposures in haemolymph. Together, our data confirm the hypothesis that supplementation with CA and/or CAF offers protection against detrimental changes associated with MMA or MA exposure in flies, being responsible, at least in part, for the protective effect of I. paraguariensis crude extract which was reported previously.

Endocrine disruptive action of diclofenac and caffeine on Astyanax altiparanae males (Teleostei: Characiformes: Characidae)

Diclofenac (DCF) and caffeine (CAF) are persistent pharmaceuticals that occur in mixtures in the aquatic ecosystems causing effects in the reproductive physiology of aquatic organisms. This study evaluated the physiological reproductive responses of Astyanax altiparanae males exposed to nominal concentrations of DCF (3.08 mg L−1) and CAF (9.59 mg L−1) separately and combined, for 96 h. The steroids profile, estrogenic biomarker vitellogenin (vtgA), testes and liver morphology, and also mortality of males were assessed. DCF and CAF degradation was 5% of the initial concentration for 24 h. The LC50 of the DCF and CAF were 30.8 mg L−1 and 95.9 mg L−1, respectively. Males exposed to DCF and CAF exhibited a reduction of 17β-Estradiol (E2) concentration compared to control (CTL). Similarly, testosterone (T) was also reduced in the DCF treatment, but this response was not observed in 11-Ketotestosterone (11-KT). Males exposed to DCF + CAF combined did not exhibit differences in T, E2 and 11-KT steroids. The vtgA gene expression and the sperm concentration did not change among the treatments. Moreover, acute exposure revealed a hypertrophy of hepatocytes cells in the DCF and DCF + CAF treatments. In conclusion, DCF and CAF, isolated, exhibit an endocrine disruptive activity in A. altiparanae male, an opposite response observed with the mixture of both compounds that abolishes the endocrine disruptive effects. DCF seems to be more toxic for this species, altering also hepatocytes morphology.

The Effect of Caffeine and Trifluralin on Chromosome Doubling in Wheat Anther Culture.

Challenges for wheat doubled haploid (DH) production using anther culture include genotype variability in green plant regeneration and spontaneous chromosome doubling. The frequency of chromosome doubling in our program can vary from 14% to 80%. Caffeine or trifluralin was applied at the start of the induction phase to improve early genome doubling. Caffeine treatment at 0.5 mM for 24 h significantly improved green plant production in two of the six spring wheat crosses but had no effect on the other crosses. The improvements were observed in Trojan/Havoc and Lancer/LPB14-0392, where green plant numbers increased by 14% and 27% to 161 and 42 green plants per 30 anthers, respectively. Caffeine had no significant effect on chromosome doubling, despite a higher frequency of doubling in several caffeine treatments in the first experiment (67–68%) compared to the control (56%). In contrast, trifluralin significantly improved doubling following a 48 h treatment, from 38% in the control to 51% and 53% in the 1 µM and 3 µM trifluralin treatments, respectively. However, trifluralin had a significant negative effect on green plant regeneration, declining from 31.8 green plants per 20 anthers (control) to 9–25 green plants per 20 anthers in the trifluralin treatments. Further work is required to identify a treatment regime with caffeine and/or anti-mitotic herbicides that consistently increases chromosome doubling in wheat without reducing green plant regeneration.

Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson’s disease

Context L-DOPA is the first-line drug for Parkinson’s disease (PD). However, chronic use can lead to dyskinesia. Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA. Objectives This study determined changes in terms of neurodegeneration, locomotion and mechanosensation in Caenorhabditis elegans (Rhabditidae) strain UA57 overexpressing tyrosine hydroxylase (CAT-2) when treated with caffeine, L-DOPA or their combinations. Materials and methods Neurodegeneration was monitored via fluorescence microscopy of GFP-tagged dopaminergic neurons in the head and tail regions of C. elegans. Meanwhile, mechanosensation and locomotion under vehicle (0.1% DMSO), L-DOPA (60 mM), caffeine (10 mM) or 60 mM L-DOPA + 10 or 20 mM caffeine (60LC10 and 60LC20) treatments were scored for 3 days (n = 20). Results L-DOPA (60 mM) reduced CEP and ADE neurons by 4.3% on day 3, with a concomitant decrease in fluorescence by 44.6%. This correlated with reductions in gentle head (−35%) and nose touch (−40%) responses, but improved locomotion (20–75%) compared with vehicle alone. CEP and ADE neuron counts were preserved with caffeine (10 mM) or 60LC10 (98–100%), which correlated with improved mechanosensation (10–23%) and locomotion (18–76%). However, none of the treatments was able to preserve PDE neuron count, reducing the basal slowing response. Discussion and conclusions Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA, which can potentially impact PD treatment and warrants further investigation.