In Vitro Evaluation of Vancomycin-Induced Toxicity in Human Primary Knee Chondrocytes.

Septic arthritis as a complication of orthopaedic joint surgery can have catastrophic outcomes for patients. To minimise infection risk associated with elective orthopaedics, topical vancomycin during surgery has become increasingly common. Evidence suggests that high concentrations of vancomycin, following direct application of the drug to the joint, are toxic towards various local cell types in the joint, including chondrocytes. However, the mechanism of this vancomycin tissue toxicity is yet to be determined. The aim of this study was to evaluate the toxicity of vancomycin on chondrocytes and the mechanisms of cell death involved. Human primary knee chondrocytes were exposed to vancomycin (1.25-10 mg/mL) for 24 h and their viability assessed using the resazurin reduction assay in vitro. Specific cell death mechanisms and their contributors, including reactive oxygen species (ROS) production and apoptosis, were measured. This study showed that high concentrations of vancomycin (5 and 10 mg/mL) were toxic towards human primary knee chondrocyte cells, while lower concentrations (1.25 and 2.5 mg/mL) were not. Cell death studies found that this occurred through an apoptotic pathway. This study provides additional support that vancomycin in high doses is toxic towards chondrocytes and preliminary evidence that this toxicity occurs via apoptotic cell death mechanisms.

Involvement of indoleamine 2, 3-dioxygenase (IDO) and brain-derived neurotrophic factor (BDNF) in the neuroprotective mechanisms of ferulic acid against depressive-like behaviour.

OBJECTIVE: Ferulic acid (FA) is a common food ingredient that is abundantly present in various routinely consumed food and beverages. Like many cinnamic acid derivatives, FA produces wide-ranging effects in a dose-dependent manner and various studies link FA consumption with reduced risk of depressive disorders. The aim of this study was to exploit the neuroprotective mechanisms of FA including indoleamine 2,3-dioxygenase (IDO), brain-derived neurotrophic factor (BDNF), and other pro-inflammatory cytokines by employing lipopolysaccharide (LPS)-induced depressive-like behaviour model. METHODS: C57BL/6J male mice were divided into 4 groups consisting of saline (SAL), LPS, FA and Imipramine (IMI). Animals were pretreated orally with FA (10 mg/kg) and IMI (10 mg/kg) for 21 days once daily and all groups except SAL were challenged with LPS (0.83 mg/kg) intraperitoneally on day 21. RESULTS: LPS administration produced a biphasic change in the behaviour of the animals where the animals lost a significant weight and express high immobility time at 24 h. Proinflammatory cytokines including, TNF-α, IL-6, IL-1ß, and IFN-γ were significantly increased along with increased lipid peroxidation and reduced BDNF. Furthermore, the increased kynurenine to tryptophan ratio was indicative of elevated IDO activity. CONCLUSION: The results of this study emphasise that low dose of FA is effective in attenuating depressive-like behaviour by modulating IDO, BDNF and reducing neuroinflammation.

Remedial effects of caffeine against depressive-like behaviour in mice by modulation of neuroinflammation and BDNF.

Objective: Caffeine (CAF) is one of the most commonly consumed nutritional stimulant in beverages. Interestingly, CAF produces varied effects in a dose-dependent manner, and that makes it one of the most controversial nutritional ingredients. Various studies have linked CAF consumption and reduced risk of depressive disorders. The aim of this study was to investigate the effect of CAF on lipopolysaccharide (LPS)-induced neuroinflammation and depressive-like behaviour.Methods: C57BL/6J male mice were divided into four groups consisting of saline (SAL), LPS, CAF and Imipramine (IMI). Animals were pretreated orally with CAF (10 mg/kg) and IMI (10 mg/kg) for 14 days once daily and all groups except SAL were challenged with LPS (0.83 mg/kg) intraperitoneally on day 14.Results: LPS produced a biphasic behavioural response with a significantly high immobility time and weight loss after 24 h. The brain cytokines (TNF-α, IL-6, IL-1ß, and IFN-γ) levels were remarkably high, along with increased lipid peroxidation and reduced Brain Derived Neurotrophic Factor (BDNF). These biochemical and behavioural changes were significantly alleviated by CAF and IMI chronic treatment.Conclusion: The results of this study implicate that mild-moderate consumption of CAF could impart anti-inflammatory properties under neuroinflammatory conditions by modulating the cytokine and neurotrophic mechanisms.

How does social context influence appraisal and help-seeking for potential cancer symptoms in adults aged 50 and over? A qualitative interview study.

OBJECTIVE: To investigate how social context and social network activation influence appraisal and help-seeking for symptoms potentially indicative of cancer. METHODS: Semi-structured telephone interview study. Community dwelling adults who had experienced at least one symptom potentially indicative of cancer within the last month were sampled from a national symptom survey. RESULTS: Thirty-four interviews were conducted. Participants looked to peers and wider society to judge whether symptoms might be normal for their age. Involvement of others in symptom appraisal promoted an active management strategy, such as contacting a healthcare professional or trying a medication. There were practical, emotional, attitudinal, normative and moral barriers to involving others. Cancer narratives from significant others, public health campaigns and the media influenced symptom appraisal. Participants held mental representations of types of people who get cancer, for example, smokers and unfit people. This had two consequences. First, participants did not identify themselves as a candidate for cancer; impeding help-seeking. Second, social judgements about lifestyle introduced stigma. CONCLUSION: Involving friends/family in symptom appraisal facilitates help-seeking but barriers exist to involving others. Campaigns to promote earlier cancer diagnosis should incorporate age-appropriate narratives, address misconceptions about 'types' of people who get cancer and tackle stigma about lifestyle factors.

Teaching Intimate Partner Violence Education: A Quasi-Experimental Study Exploring Gaming and Storytelling.

ABSTRACT: The purpose of this quasi-experimental study was to evaluate best strategies for teaching intimate partner violence (IPV) education in an undergraduate community health nursing course. Results suggest gaming was a more effective strategy than storytelling for knowledge acquisition and storytelling was more effective for knowledge retention. IPV-related nursing interventions can impact client outcomes; therefore, education is needed prior to entering the workforce. The evaluation of strategies to improve knowledge acquisition and retention of IPV content is essential to ensure best practices for detection and intervention.

British Association of Urological Surgeons suprapubic catheter practice guidelines - revised.

AIMS: To report the updated and revised British Association of Urological Surgeons (BAUS) guideline on indications, safe insertion and subsequent care of suprapubic catheters (SPCs). METHODS: The existing BAUS guideline on the insertion of SPCs was reviewed and has been updated in light of both activity and outcome data published since the original guideline was written. A systematic review of all new data from 2010 onwards was carried out. This updated guideline is largely evidence-based but, where evidence was lacking, is based on the consensus of expert opinion from members of the BAUS Section of Female, Neurological and Urodynamic Urology. RESULTS: Suprapubic catheterization is widely used and generally considered a safe procedure. There is, however, a small risk of serious complications including bowel injury. The BAUS has produced an updated consensus statement on SPC use with the aim of minimizing risks and establishing best practice. Areas for future research and development are also highlighted. This review has been commissioned and approved by the BAUS and the Section of Female, Neurological and Urodynamic Urology. CONCLUSIONS: While SPC insertion is generally regarded as a safe procedure, the risk of serious morbidity and death must always be considered and outlined to patients. These revised guidelines should assist in minimizing the morbidity associated with SPC usage.

Non-prescription medicines may contribute to non-adherence to prescription medicines in people living with chronic health conditions.

BACKGROUND: Non-adherence to prescribed medicines is linked to adverse health outcomes in people living with chronic health conditions (CHCs). Multiple factors are known to contribute to non-adherence to medicines including polypharmacy, demographic features and disease and health systems. Both non-prescription and prescription medicines contribute to polypharmacy; however, there is limited data on the influence of non-prescription medicines to non-adherence. AIM: Therefore, the aim of the study was to investigate the influence of non-prescription medicines to non-adherence in an Australian population. METHODS: Data from the 2016 National Survey of a random sample of Australian adult residents were utilised in this study to investigate factors associated with non-adherence. Descriptive statistics, χ2 , regression and generalised linear models were used to assess the relationships between variables of interest. Narrative response and comments were used to provide further insight. RESULTS: This study recruited 1217 participants to explore factors associated with non-adherence to medicines. Weak but statistically significant correlations were identified showing the number of CHCs, patient's age, number of prescription medicines, number of non-prescription medicines and total number of medicines associated with non-adherence. DISCUSSION: The findings suggest that people living with CHCs and taking multiple medicines, including non-prescription medicines, are likely to be non-adherent to prescription medicines. This study shows the possible involvement of non-prescription medicines in contributing to non-adherence in an Australian population and suggests that future studies with a broader demographic are warranted.

Trichloroethylene exposure alters dimethylated histone three lysine four in protein kinase A signaling pathway chromatin of rat sperm†.

Histone three lysine four dimethylation (H3k4me2) in sperm is conserved across species and is linked to transgenerational epigenetic inheritance. To test whether H3K4me2 is a target for transgenerational inheritance of toxicity, a daily gavage bolus exposure of trichloroethylene (TCE) (1000 mg/kg/day) was given to rats for 14 weeks, then epididymal sperm were isolated and native chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) of H3K4me2 was performed. Differential region analysis determined there were 2608 significantly differential H3K4me2 regions after TCE exposure, 477 were significantly increased and 2131 were significantly decreased. Z-score enrichment of differential regions determined there were significantly decreased H3k4me2 in the coding and regulatory regions of genes in the PKA signaling pathway. These changes account for TCE induced spermatozoal toxicity and show H3K4me2 is a target for paternal inheritance of toxicity.

Beyond pros and cons - developing a patient decision aid to cultivate dialog to build relationships: insights from a qualitative study and decision aid development.

BACKGROUND: An individualized approach using shared decision-making (SDM) and goal setting is a person-centred strategy that may facilitate prioritization of treatment options. SDM has not been adopted extensively in clinical practice. An interprofessional approach to SDM with tools to facilitate patient participation may overcome barriers to SDM use. The aim was to explore decision-making experiences of health professionals and people with diabetes (PwD), then develop an intervention to facilitate interprofessional shared decision-making (IP-SDM) and goal-setting. METHODS: This was a multi-phased study. 1) Feasibility: Using a descriptive qualitative study, individual interviews with primary care physicians, nurses, dietitians, pharmacists, and PwD were conducted. The interviews explored their experiences with SDM and priority-setting, including facilitators and barriers, relevance of a decision aid for priority-setting, and integration of SDM and a decision aid into practice. 2) Development: An evidence-based SDM toolkit was developed, consisting of an online decision aid, MyDiabetesPlan, and implementation tools. MyDiabetesPlan was reviewed by content experts for accuracy and comprehensiveness. Usability assessment was done with 3) heuristic evaluation and 4) user testing, followed by 5) refinement. RESULTS: Seven PwD and 10 clinicians participated in the interviews. From interviews with PwD, we identified that: (1) approaches to decision-making were diverse and dynamic; (2) a trusting relationship with the clinician and dialog were critical precursors to SDM; and, (3) goal-setting was a dynamic process. From clinicians, we found: (1) complementary (holistic and disease specific) approaches to the complex patient were used; (2) patient-provider agendas for goal-setting were often conflicting; (3) a flexible approach to decision-making was needed; and, (4) conflict could be resolved through SDM. Following usability assessment, we redesigned MyDiabetesPlan to consist of data collection and recommendation stages. Findings were used to finalize a multi-component toolkit and implementation strategy, consisting of MyDiabetesPlan, instructional card and videos, and orientation meetings with participating patients and clinicians. CONCLUSIONS: A decision aid can provide information, facilitate clinician-patient dialog and strengthen the therapeutic relationship. Implementation of the decision aid can fit into a model of team care that respects and exemplifies professional identity, and can facilitate intra-team communication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02379078. Date of Registration: 11 February 2015.

Caffeine content of Nespresso® pod coffee.

BACKGROUND:: Little independent information on the caffeine content of the popular Nespresso® coffee pod range exists. AIM:: To quantify the caffeine content of Nespresso® pod coffees. METHODS:: Initially, three serves (ristretto (S), espresso (M), lungo (L)) of two pod varieties (Livanto and Roma) were prepared on three different Nespresso® machines (2 × U-Delonghi (1 × 5 years since purchase (old), 1 × recently purchased (new)), 1 × new Lattissima Pro (alternate)) using two different batches (sleeves). Caffeine content was then determined via triplicate samples using high-performance liquid chromatography. Differences in content (i.e. serve size, machine or sleeve) were determined via an analysis of variance or paired sample t-tests. RESULTS:: Coffees prepared on different machines or pods from different sleeves did not influence the caffeine content (old = 63 ± 13, new = 60 ± 8, alternate = 60 ± 10 mg·serve-1; p = 0.537, sleeveA = 63 ± 11, sleeveB = 59 ± 9 mg·serve-1; p = 0.134). Less caffeine was delivered in S (51 ± 7 mg·serve-1) compared to larger sizes (M = 66 ± 7 and L = 66 ± 10 mg·serve-1). Subsequently, the caffeine content from two serve sizes (S and L) from 17 other varieties within the Nespresso® range was determined and compared to the manufacturer's values. Caffeine content (all pods) ranged from 19 to 147 mg·serve-1, and represented 51-162% of manufacturer's values. CONCLUSION:: Nespresso® consumers are exposed to variable amounts of caffeine, which often differ from the manufacturer's reports.

Possible involvement of metformin in downregulation of neuroinflammation and associated behavioural changes in mice.

Metformin (MET), a biguanide oral hypoglycaemic agent, recently has been shown to be effective in various conditions other than type-2 diabetes including cancer, stroke, weight reduction, and polycystic ovarian syndrome, to name a few. MET has also possessed antioxidant and antiinflammatory properties by activation of AMPK . This study was aimed at evaluating the effects of MET on lipopolysaccharide (LPS)-induced systemic and neuroinflammation, oxidative stress, and behavioural changes. The study consisted of six groups, where three selected doses of MET (100, 200, and 300 mg/kg) were employed in male Swiss albino mice, with one group of imipramine (IMI), saline, and LPS each. Systemic inflammation was induced by injecting LPS (1.5 mg/kg) by intraperitoneal route. A battery of behavioural tests including open field, forced swim, and tail suspension tests were employed to assess the impact of systemic inflammation on exploratory behaviour and learned helplessness. LPS induced significant immobility with profound symptoms of sickness behaviour. Furthermore, LPS led to significant increase in serum and brain proinflammatory cytokines TNF-α and IL-6; and also increased lipid peroxidation with reduced glutathione levels. Pretreatment of the animals with 100 and 200 mg/kg of MET significantly reduced both systemic and central inflammatory markers along with protecting against LPS-induced oxidative stress. The higher dose, 300 mg/kg of MET was not effective against most of LPS-induced biochemical changes. Our preliminary results from this study suggest the antiinflammatory and neuroprotective effects of MET in LPS-induced model of sickness behaviour and neuroinflammation.

Localization of dimethylated histone three lysine four in the Rattus norvegicus sperm genome.

We examined the precise localization of dimethylated histone three lysine four (H3K4me2) in mature rat sperm. Within nonintergenic-enriched regions, half of the DNA peaks associated with H3K4me2 retention fell in gene bodies and the other half in promoter regions. The most significant peaks near annotated DNA regions in the composite data included loci known to be associated with RNA metabolism, cell cycle regulation, and spermatogenesis. Regions associated with differential retention of H3K4me2 within gene bodies were significantly enriched for housekeeping gene and cell-cycle functionality. Proximal promoter-associated peaks were enriched for viral reproduction and cell cycle regulation genes, while Promoter1k and Promoter3k peaks were enriched for RNA metabolism functions. Further, homeobox- and kruppel-like factor motifs were among the most significantly enriched de novo and known motifs discovered within gene-associated H3K4me2 peaks. Motif analysis and native chromatin immunoprecipitation followed by sequencing (nChIP-seq) peak calling indicated an instructive role for retained paternal histones in the epigenetic regulation of early embryonic development in the rat.

Effects of continuous bisphenol A exposure from early gestation on 90 day old rat testes function and sperm molecular profiles: A CLARITY-BPA consortium study.

Bisphenol A (BPA) is a ubiquitous industrial chemical that has been identified as an endocrine disrupting compound (EDC). There is growing concern that early life exposures to EDCs, such as BPA, can adversely affect the male reproductive tract and function. This study was conducted as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) to further delineate the toxicities associated with continuous exposure to BPA from early gestation, and to comprehensively examine the elicited effects on testes and sperm. NCTR Sprague Dawley rat dams were gavaged from gestational day (GD) 6 until parturition, and their pups were directly gavaged daily from postnatal day (PND) 1 to 90 with BPA (2.5, 25, 250, 2500, 25,000, 250,000 µg/kg/d) or vehicle control. At PND 90, the testes and sperm were collected for evaluation. The testes were histologically evaluated for altered germ cell apoptosis, sperm production, and altered spermiation. RNA and DNA isolated from sperm were assessed for elicited changes in global mRNA transcript abundance and altered DNA methylation. Effects of BPA were observed in changes in body, testis and epididymis weights only at the highest administered dose of BPA of 250,000 µg/kg/d. Genome-wide transcriptomic and epigenomic analyses failed to detect robust alterations in sperm mRNA and DNA methylation levels. These data indicate that prolonged exposure starting in utero to BPA over a wide range of levels has little, if any, impact on the testes and sperm molecular profiles of 90 day old rats as assessed by the histopathologic, morphometric, and molecular endpoints evaluated.

Interplay between adenosine receptor antagonist and cyclooxygenase inhibitor in haloperidol-induced extrapyramidal effects in mice.

Antipsychotic drugs are the mainstay of psychotic disorders. The 'typical' antipsychotic agents are commonly employed for the positive symptoms of schizophrenia, though at an expense of extrapyramidal side effects (EPS). In the present study, we employed haloperidol (HP)-induced catalepsy model in mice to evaluate the role of adenosine receptor antagonist and cyclooxygenase (COX) enzyme inhibitor in the amelioration of EPS. HP produced a full blown catalepsy, akinesia and a significant impairment in locomotion and antioxidant status. Pre-treatment with COX inhibitor; naproxen (NPx) and adenosine receptor antagonist; caffeine (CAF), showed a significant impact on HP-induced cataleptic symptoms. Adenosine exerts pivotal control on dopaminergic receptors and is also involved in receptor internalization and recycling. On the other hand, prostaglandins (PGs) are implicated as neuro-inflammatory molecules released due to microglial activation in both Parkinson's disease (PD) and antipsychotics-induced EPS. The involvement of these neuroeffector molecules has led to the possibility of use of CAF and COX inhibitors as therapeutic approaches to reduce the EPS burden of antipsychotic drugs. Both these pathways seem to be interlinked to each other, where adenosine modulates the formation of PGs through transcriptional modulation of COXs. We observed an additive effect with combined treatment of NPx and CAF against HP-induced movement disorder. These effects lead us to propose that neuromodulatory pathways of dopaminergic circuitry need to be explored for further understanding and utilizing the full therapeutic potential of antipsychotic agents.

Prostanoid EP2 Receptors Are Up-Regulated in Human Pulmonary Arterial Hypertension: A Key Anti-Proliferative Target for Treprostinil in Smooth Muscle Cells.

Prostacyclins are extensively used to treat pulmonary arterial hypertension (PAH), a life-threatening disease involving the progressive thickening of small pulmonary arteries. Although these agents are considered to act therapeutically via the prostanoid IP receptor, treprostinil is the only prostacyclin mimetic that potently binds to the prostanoid EP2 receptor, the role of which is unknown in PAH. We hypothesised that EP2 receptors contribute to the anti-proliferative effects of treprostinil in human pulmonary arterial smooth muscle cells (PASMCs), contrasting with selexipag, a non-prostanoid selective IP agonist. Human PASMCs from PAH patients were used to assess prostanoid receptor expression, cell proliferation, and cyclic adenosine monophosphate (cAMP) levels following the addition of agonists, antagonists or EP2 receptor small interfering RNAs (siRNAs). Immunohistochemical staining was performed in lung sections from control and PAH patients. We demonstrate using selective IP (RO1138452) and EP2 (PF-04418948) antagonists that the anti-proliferative actions of treprostinil depend largely on EP2 receptors rather than IP receptors, unlike MRE-269 (selexipag-active metabolite). Likewise, EP2 receptor knockdown selectively reduced the functional responses to treprostinil but not MRE-269. Furthermore, EP2 receptor levels were enhanced in human PASMCs and in lung sections from PAH patients compared to controls. Thus, EP2 receptors represent a novel therapeutic target for treprostinil, highlighting key pharmacological differences between prostacyclin mimetics used in PAH.

Pyocyanin induces systemic oxidative stress, inflammation and behavioral changes in vivo.

Pyocyanin (PCN) is a virulence factor secreted by Pseudomonas aeruginosa (P. aeruginosa) that has been shown to have numerous toxic effects in both in vitro and in vivo studies. Such toxicities include pro-inflammatory and pro-oxidant mediated responses. It is hypothesized that PCN can cross biological membranes and reach the systemic circulation, but no previous studies have investigated this. The aim of this study was, therefore, to quantify PCN in plasma and assess if systemic responses were occurring after localized intranasal administration in C57BL/6 J mice. This was achieved through the plasma quantification of PCN and assessment of changes to behavior using two commonly used tests, the forced swimming test and the open field test. Furthermore, evidence of systemic oxidative stress and inflammation was measured using malondialdehyde (MDA) and TNF-α post PCN exposure. PCN was found to cross into systemic circulation but in a variable manner. Furthermore, significant increases in plasma TNF-α and MDA (both p < 0.001) were observed along with changes in behavior indicative of systemic inflammatory responses.

Identification of sperm mRNA biomarkers associated with testis injury during preclinical testing of pharmaceutical compounds.

The human testis is sensitive to toxicant-induced injury but current methods for detecting adverse effects are limited, insensitive and unreliable. Animal studies use sensitive histopathological endpoints to assess toxicity, but require testicular tissue that is not available during human clinical trials. More sensitive and reliable molecular biomarkers of testicular injury are needed to better monitor testicular toxicity in both clinical and preclinical. Adult male Wistar Han rats were exposed for 4weeks to compounds previously associated with testicular injury, including cisplatin (0, 0.2, 0.3, or 0.4mg/kg/day), BI665915 (0, 20, 70, 100mg/kg/d), BI665636 (0, 20, 100mg/kg/d) or BI163538 (0, 70, 150, 300mg/kg/d) to evaluate reproductive toxicity and assess changes in sperm mRNA levels. None of the compounds resulted in any significant changes in body, testis or epididymis weights, nor were there decreases in testicular homogenization resistant spermatid head counts. Histopathological evaluation found that only BI665915 treatment caused any testicular effects, including minor germ cell loss and disorganization of the seminiferous tubule epithelium, and an increase in the number of retained spermatid heads. A custom PCR-array panel was used to assess induced changes in sperm mRNA. BI665915 treatment resulted in a significant increase in clusterin (Clu) levels and decreases in GTPase, IMAP family member 4 (Gimap4), prostaglandin D2 synthase (Ptgds) and transmembrane protein with EGF like and two follistatin like domains 1 (Tmeff1) levels. Correlation analysis between transcript levels and quantitative histopathological endpoints found a modest association between Clu with retained spermatid heads. These results demonstrate that sperm mRNA levels are sensitive molecular indicators of testicular injury that can potentially be translated into a clinical setting.

The pregnant urologist.

Female urologists represent an ever-increasing percentage of the work force; more and more of our colleagues will be working through pregnancy. There is a lack of clear and concise advice for pregnant urologists about occupational risks during pregnancy. Urology exposes expectant mothers to potential risks from radiation, teratogenic and cytotoxic drugs, iodine hand scrub, infections, and long working hours. We aim to provide a review of the current evidence and guidance to aid expectant mothers in their decision making. Relevant research articles and up-to-date guidance were reviewed. The millisevert (the average accumulated background radiation dose to an individual for 1 year, exclusive of radon) was used as the main unit of radiation dose. There is no published evidence to date in pregnant clinicians that shows a received radiation dose of more than the recommended dose for a pregnant lady, and no data showing an increased risk of foetal abnormalities in clinicians who continue to screen during pregnancy; however, the data are from small studies. There is strong advice suggesting avoidance of contact with crushed or broken 5α-reductase inhibitor tablets (finasteride and dutasteride), mitomycin and other cytotoxic drugs during pregnancy. Pregnant surgeons should avoid frequent use of iodine hand wash. Good hygiene precautions will protect from many infections along with up-to-date immunisations and use of personal protective equipment for certain cases.

Modulation of chemotherapy-induced cytotoxicity in SH-SY5Y neuroblastoma cells by caffeine and chlorogenic acid.

Chemotherapy is an important treatment modality for malignancy but is limited by significant toxicity and it susceptibility to numerous drug interactions. While the interacting effects with medications are well known, there is limited evidence on the interaction with commonly consumed food and natural products. The aim of this study was to evaluate the bioactive constituents of coffee (caffeine and chlorogenic acid) on the cytotoxicity of doxorubicin, gemcitabine, and paclitaxel in vitro. Pretreatment with caffeine (100 nM and 10 µM) sensitized SH-SY5Y cells to doxorubicin-induced toxicity and increased apoptosis and sensitized PC3 cells to gemcitabine-induced toxicity. Pretreatment with 10 µM caffeine decreased total cell reactive oxygen species (ROS) production but increased mitochondrial ROS production. In contrast, caffeine (10 nM and 10 µM) protected cells against gemcitabine-induced toxicity and apoptosis. Similarly, 1 µM and 10 µM caffeine protected cells against paclitaxel-induced toxicity and mitochondrial ROS production. Chlorogenic acid had no effect on chemotherapy-induced toxicity in SH-SY5Y cells. In conclusion, this study provides preliminary evidence that caffeine, not chlorogenic acid, modulates the cytotoxicity of doxorubicin, gemcitabine, and paclitaxel in SH-SY5Y cells via different mechanisms.